Anne I. Sperling

Research Summary
Dr. Sperling is Professor of Medicine, Associate Vice Chair for Research of the Dept of Medicine, Director of the Respiratory Biology Training Grant, and Director of the Cytometry and Antibody Technology Core Facility. She has served as a regular member of the NIH Hypersensitivity, Autoimmunity, and Immune-mediated Diseases (HAI) Study Section, and the Lung Cellular and Molecular Immunology (LCMI) Study Section. Dr. Sperling's research program focuses on the role of the immune system in lung diseases in humans and mouse models. She has made significant contributions to understanding how T cell costimulatory molecules influence inflammation and disease, and the regulation of inflammation resolution in allergic asthma. Recently, her group has been expanding its focus to address translational and basic questions in human lung diseases such as asthma, idiopathic pulmonary fibrosis, and sarcoidosis. Research Statement: The focus of my laboratory is to elucidate on the immune response characteristic of lung diseases such as atopic asthma and idiopathic pulmonary fibrosis. While in the past we focused highly on the resolution of airway inflammation (Tong et al JEM 2006 and Tong et al AJRCMB 2010), the current research is focused on the initial steps in the development of Th2 inflammation. Our goal is to determine how specific allergic stimuli signals the immune response to drive type 2 inflammation and Th2 differentiation. We have recently made three important discoveries that elucidate mechanisms involved in sensitization to allergens in the lungs. Our first finding is that allergen specific IgG in immune complexes with allergen, can directly induce dendritic cells to produce the Th2 promoting cytokine, IL-33 (Tjota et al JCI 2013). Through recent GWAS studies, IL-33 and its receptor have recently been found to be in the top five genes involved in asthma. We have found that a major source of IL-33 in various Th2 inflammatory models is the respiratory DC. Further, we have now found that this IL-33 production is essential for Th2 mediated inflammation in our models. Second, we have made the exciting discovery that the transcription factor, Interferon Regulatory Factor 4 (IRF4) directs dendritic cells to promote TH2 responses (Williams et al Nature Comm 2013). Respiratory dendritic cells (DC) are the primary initiator of T cells during lung allergic responses. DCs process inhaled allergen, traffic to draining lymph nodes, present antigen-peptides to T cells, and guide the type of T-helper response initiated. However, the mechanisms involved in priming a DC to direct Th2 helper cell differentiation have not yet been elucidated. We now believe that we have identified a key transcription factor that when expressed in DCs, confers the ability of the DC to drive Th2 immunity in the lungs. Using microarray analsysis, we identified this transcription factor as being expressed in the Th2 driving DCs, but not in other DC populations. Additionally, mice with a conditional deletion of IRF4 in DCs produce a much reduced Th2 responses after allergic challenge, while DCs with overexpression of IRF4 drive naïve CD4 T lymphocytes toward a Th2 phenotype. Thus, these data identify IRF4 as a key transcriptional regulator in DCs necessary for the development of Th2 responses. Third, we have discovered that two distinct Th2 stimuli, Immune Complexes and HDM, both utilize FcR-gamma associated receptors, Fc-gammaRIII and Dectin-2 respectively, to promote Th2-mediated lung inflammation (Tjota et al. JACI 2014). We have demonstrated that both ICs and HDM induce expression of IL-33, a critical mediator in asthma pathogenesis and the differentiation of Th2 cells, in DCs. Upregulation of IL-33 in DCs is dependent on FcR-gamma, toll-like receptor 4 (TLR4), and phosphoinositide 3 (PI3)-kinase. Exogenous IL-33 is sufficient to restore development of Th2 responses in FcR-gamma-deficient mice. Finally, adoptive transfer of allergen-pulsed FcR-gamma+/- BMDCs restores development of Th2-type inflammation in FcR-gamma-deficient mice, demonstrating the necessity of this signaling pathway in DCs for allergen-induced inflammation. Together, these data identify a mechanism whereby Th2 stimuli signal through FcR-gamma-associated receptors on DCs to induce IRF4 expression and upregulation of IL-33 production. These DCs cells are central to the induction of Th2-differentiation and type 2 allergic airway inflammation. Dr. Sperling's NIH Commons ID is ASPERLING
Keywords
Asthma, Pulmonary Fibrosis, T Cells, Dendritic Cells, Lung Inflammation, Lung Injury
Education
  • University of Chicago, Chicago, IL, Postdoctoral Fellowship 1994
  • Tufts University, Boston, MA, PhD Immunology 1990
  • Smith College, Northampton,MA, A.B. Biology 1984
Biosciences Graduate Program Association
Publications
  1. Schoettler N, Hrusch CL, Blaine KM, Sperling AI, Ober C. Transcriptional programming and T cell receptor repertoires distinguish human lung and lymph node memory T cells. Commun Biol. 2019; 2:411. View in: PubMed

  2. Alqalyoobi S, Adegunsoye A, Linderholm A, Hrusch C, Cutting C, Ma SF, Sperling A, Noth I, Strek ME, Oldham JM. Circulating Plasma Biomarkers of Progressive Interstitial Lung Disease. Am J Respir Crit Care Med. 2019 Sep 16. View in: PubMed

  3. Hrusch CL, Stein MM, Gozdz J, Holbreich M, von Mutius E, Vercelli D, Ober C, Sperling AI. T-cell phenotypes are associated with serum IgE levels in Amish and Hutterite children. J Allergy Clin Immunol. 2019 Nov; 144(5):1391-1401.e10. View in: PubMed

  4. Tighe RM, Redente EF, Yu YR, Herold S, Sperling AI, Curtis JL, Duggan R, Swaminathan S, Nakano H, Zacharias WJ, Janssen WJ, Freeman CM, Brinkman RR, Singer BD, Jakubzick CV, Misharin AV. Improving the Quality and Reproducibility of Flow Cytometry in the Lung. An Official American Thoracic Society Workshop Report. Am J Respir Cell Mol Biol. 2019 Aug; 61(2):150-161. View in: PubMed

  5. Sharma A, Laxman B, Naureckas ET, Hogarth DK, Sperling AI, Solway J, Ober C, Gilbert JA, White SR. Associations between fungal and bacterial microbiota of airways and asthma endotypes. J Allergy Clin Immunol. 2019 Nov; 144(5):1214-1227.e7. View in: PubMed

  6. White SR, Laxman B, Naureckas ET, Hogarth DK, Solway J, Sperling AI, Ober C. Evidence for an IL-6-high asthma phenotype in asthmatic patients of African ancestry. J Allergy Clin Immunol. 2019 Jul; 144(1):304-306.e4. View in: PubMed

  7. Krishack PA, Louviere TJ, Decker TS, Kuzel TG, Greenberg JA, Camacho DF, Hrusch CL, Sperling AI, Verhoef PA. Protection against Staphylococcus aureus bacteremia-induced mortality depends on ILC2s and eosinophils. JCI Insight. 2019 Mar 21; 4(6). View in: PubMed

  8. Adegunsoye A, Oldham JM, Sperling AI, Noth I, Strek ME, Chung JH. Reply to Lescoat et al. and to Khamis et al. Am J Respir Crit Care Med. 2019 Apr 15; 199(8):1041-1042. View in: PubMed

  9. Reyfman PA, Walter JM, Joshi N, Anekalla KR, McQuattie-Pimentel AC, Chiu S, Fernandez R, Akbarpour M, Chen CI, Ren Z, Verma R, Abdala-Valencia H, Nam K, Chi M, Han S, Gonzalez-Gonzalez FJ, Soberanes S, Watanabe S, Williams KJN, Flozak AS, Nicholson TT, Morgan VK, Winter DR, Hinchcliff M, Hrusch CL, Guzy RD, Bonham CA, Sperling AI, Bag R, Hamanaka RB, Mutlu GM, Yeldandi AV, Marshall SA, Shilatifard A, Amaral LAN, Perlman H, Sznajder JI, Argento AC, Gillespie CT, Dematte J, Jain M, Singer BD, Ridge KM, Lam AP, Bharat A, Bhorade SM, Gottardi CJ, Budinger GRS, Misharin AV. Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019 Jun 15; 199(12):1517-1536. View in: PubMed

  10. Williams JW, Ferreira CM, Blaine KM, Rayon C, Velázquez F, Tong J, Peter ME, Sperling AI. Non-apoptotic Fas (CD95) Signaling on T Cells Regulates the Resolution of Th2-Mediated Inflammation. Front Immunol. 2018; 9:2521. View in: PubMed

  11. Ferreira CM, Williams JW, Tong J, Rayon C, Blaine KM, Sperling AI. Allergen Exposure in Lymphopenic Fas-Deficient Mice Results in Persistent Eosinophilia Due to Defects in Resolution of Inflammation. Front Immunol. 2018; 9:2395. View in: PubMed

  12. Adegunsoye A, Oldham JM, Bonham C, Hrusch C, Nolan P, Klejch W, Bellam S, Mehta U, Thakrar K, Pugashetti JV, Husain AN, Montner SM, Straus CM, Vij R, Sperling AI, Noth I, Strek ME, Chung JH. Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation. Am J Respir Crit Care Med. 2019 Mar 15; 199(6):747-759. View in: PubMed

  13. Stein MM, Hrusch CL, Sperling AI, Ober C. Effects of an Fc?RIIA polymorphism on leukocyte gene expression and cytokine responses to anti-CD3 and anti-CD28 antibodies. Genes Immun. 2019 07; 20(6):462-472. View in: PubMed

  14. Greenberg JA, Hrusch CL, Jaffery MR, David MZ, Daum RS, Hall JB, Kress JP, Sperling AI, Verhoef PA. Distinct T-helper cell responses to Staphylococcus aureus bacteremia reflect immunologic comorbidities and correlate with mortality. Crit Care. 2018 Apr 25; 22(1):107. View in: PubMed

  15. Tjota MY, Camacho DF, Turnquist HR, Sperling AI. IL-33 Drives Monocyte Recruitment to Lung Interstitium through Chemokine Upregulation. Immunohorizons. 2017 Aug 01; 1(6):101-108. View in: PubMed

  16. Krishack PA, Wang K, Rzhetsky A, Solway J, Sperling AI, Verhoef PA. Preexisting Type 2 Immune Activation Protects against the Development of Sepsis. Am J Respir Cell Mol Biol. 2017 11; 57(5):628-630. View in: PubMed

  17. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, Amigorena S, Van't Veer LJ, Sperling AI, Wolf DM, Krummel MF. Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity. Cancer Cell. 2014 Dec 08; 26(6):938. View in: PubMed

  18. Ober C, Sperling AI, von Mutius E, Vercelli D. Immune development and environment: lessons from Amish and Hutterite children. Curr Opin Immunol. 2017 Oct; 48:51-60. View in: PubMed

  19. Hrusch CL, Manns ST, Bryazka D, Casaos J, Bonham CA, Jaffery MR, Blaine KM, Mills KAM, Verhoef PA, Adegunsoye AO, Williams JW, Tjota MY, Moore TV, Strek ME, Noth I, Sperling AI. ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s. Mucosal Immunol. 2018 01; 11(1):61-70. View in: PubMed

  20. White SR, Nicodemus-Johnson J, Laxman B, Denner DR, Naureckas ET, Hogarth DK, Stern R, Minc A, Solway J, Sperling A, Ober C. Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma. J Allergy Clin Immunol. 2017 09; 140(3):857-860. View in: PubMed

  21. Nicodemus-Johnson J, Myers RA, Sakabe NJ, Sobreira DR, Hogarth DK, Naureckas ET, Sperling AI, Solway J, White SR, Nobrega MA, Nicolae DL, Gilad Y, Ober C. DNA methylation in lung cells is associated with asthma endotypes and genetic risk. JCI Insight. 2016 12 08; 1(20):e90151. View in: PubMed

  22. Adegunsoye A, Hrusch CL, Bonham CA, Jaffery MR, Blaine KM, Sullivan M, Churpek MM, Strek ME, Noth I, Sperling AI. Skewed Lung CCR4 to CCR6 CD4+ T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function. Front Immunol. 2016; 7:516. View in: PubMed

  23. Stein MM, Hrusch CL, Gozdz J, Igartua C, Pivniouk V, Murray SE, Ledford JG, Marques Dos Santos M, Anderson RL, Metwali N, Neilson JW, Maier RM, Gilbert JA, Holbreich M, Thorne PS, Martinez FD, von Mutius E, Vercelli D, Ober C, Sperling AI. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. N Engl J Med. 2016 Aug 04; 375(5):411-421. View in: PubMed

  24. Kariuki SN, Maranville JC, Baxter SS, Jeong C, Nakagome S, Hrusch CL, Witonsky DB, Sperling AI, Di Rienzo A. Mapping Variation in Cellular and Transcriptional Response to 1,25-Dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells. PLoS One. 2016; 11(7):e0159779. View in: PubMed

  25. Gozdz J, Holbreich M, Metwali N, Thorne PS, Sperling AI, Martinez FD, Ober C, von Mutius E, Vercelli D. Amish and Hutterite Environmental Farm Products Have Opposite Effects on Experimental Models of Asthma. Ann Am Thorac Soc. 2016 Mar; 13 Suppl 1:S99. View in: PubMed

  26. Denner DR, Sangwan N, Becker JB, Hogarth DK, Oldham J, Castillo J, Sperling AI, Solway J, Naureckas ET, Gilbert JA, White SR. Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways. J Allergy Clin Immunol. 2016 05; 137(5):1398-1405.e3. View in: PubMed

  27. Verhoef PA, Constantinides MG, McDonald BD, Urban JF, Sperling AI, Bendelac A. Intrinsic functional defects of type 2 innate lymphoid cells impair innate allergic inflammation in promyelocytic leukemia zinc finger (PLZF)-deficient mice. J Allergy Clin Immunol. 2016 Feb; 137(2):591-600.e1. View in: PubMed

  28. Nicodemus-Johnson J, Naughton KA, Sudi J, Hogarth K, Naurekas ET, Nicolae DL, Sperling AI, Solway J, White SR, Ober C. Genome-Wide Methylation Study Identifies an IL-13-induced Epigenetic Signature in Asthmatic Airways. Am J Respir Crit Care Med. 2016 Feb 15; 193(4):376-85. View in: PubMed

  29. Edelblum KL, Singh G, Odenwald MA, Lingaraju A, El Bissati K, McLeod R, Sperling AI, Turner JR. ?d Intraepithelial Lymphocyte Migration Limits Transepithelial Pathogen Invasion and Systemic Disease in Mice. Gastroenterology. 2015 Jun; 148(7):1417-26. View in: PubMed

  30. Sperling AI, Ansel KM. Editorial overview: Allergy and hypersensitivity. Curr Opin Immunol. 2014 Dec; 31:ix-xi. View in: PubMed

  31. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, Amigorena S, Van't Veer LJ, Sperling AI, Wolf DM, Krummel MF. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 2014 Nov 10; 26(5):638-52. View in: PubMed

  32. Hrusch CL, Tjota MY, Sperling AI. The role of dendritic cells and monocytes in the maintenance and loss of respiratory tolerance. Curr Allergy Asthma Rep. 2015 Jan; 15(1):494. View in: PubMed

  33. Tjota MY, Sperling AI. Distinct dendritic cell subsets actively induce Th2 polarization. Curr Opin Immunol. 2014 Dec; 31:44-50. View in: PubMed

  34. Tjota MY, Hrusch CL, Blaine KM, Williams JW, Barrett NA, Sperling AI. Signaling through FcR?-associated receptors on dendritic cells drives IL-33-dependent TH2-type responses. J Allergy Clin Immunol. 2014 Sep; 134(3):706-713.e8. View in: PubMed

  35. Flor AC, Williams JH, Blaine KM, Duggan RC, Sperling AI, Schwartz DA, Kron SJ. DNA-directed assembly of antibody-fluorophore conjugates for quantitative multiparametric flow cytometry. Chembiochem. 2014 Jan 24; 15(2):267-75. View in: PubMed

  36. Williams JW, Tjota MY, Clay BS, Vander Lugt B, Bandukwala HS, Hrusch CL, Decker DC, Blaine KM, Fixsen BR, Singh H, Sciammas R, Sperling AI. Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation. Nat Commun. 2013; 4:2990. View in: PubMed

  37. Cannon JL, Asperti-Boursin F, Letendre KA, Brown IK, Korzekwa KE, Blaine KM, Oruganti SR, Sperling AI, Moses ME. PKC? regulates T cell motility via ezrin-radixin-moesin localization to the uropod. PLoS One. 2013; 8(11):e78940. View in: PubMed

  38. Chen B, Moore TV, Li Z, Sperling AI, Zhang C, Andrade J, Rodriguez A, Bahroos N, Huang Y, Morrisey EE, Gruber PJ, Solway J. Gata5 deficiency causes airway constrictor hyperresponsiveness in mice. Am J Respir Cell Mol Biol. 2014 Apr; 50(4):787-95. View in: PubMed

  39. Williams JW, Yau D, Sethakorn N, Kach J, Reed EB, Moore TV, Cannon J, Jin X, Xing H, Muslin AJ, Sperling AI, Dulin NO. RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2013 Nov 15; 305(10):L693-701. View in: PubMed

  40. Wu Q, Gardiner GJ, Berry E, Wagner SR, Lu T, Clay BS, Moore TV, Ferreira CM, Williams JW, Luster AD, Medoff BD, Cannon JL, Sperling AI, Shilling RA. ICOS-expressing lymphocytes promote resolution of CD8-mediated lung injury in a mouse model of lung rejection. PLoS One. 2013; 8(8):e72955. View in: PubMed

  41. Tjota MY, Williams JW, Lu T, Clay BS, Byrd T, Hrusch CL, Decker DC, de Araujo CA, Bryce PJ, Sperling AI. IL-33-dependent induction of allergic lung inflammation by Fc?RIII signaling. J Clin Invest. 2013 May; 123(5):2287-97. View in: PubMed

  42. Kach J, Sandbo N, Sethakorn N, Williams J, Reed EB, La J, Tian X, Brain SD, Rajendran K, Krishnan R, Sperling AI, Birukov K, Dulin NO. Regulation of myofibroblast differentiation and bleomycin-induced pulmonary fibrosis by adrenomedullin. Am J Physiol Lung Cell Mol Physiol. 2013 Jun 01; 304(11):L757-64. View in: PubMed

  43. Nicodemus-Johnson J, Laxman B, Stern RK, Sudi J, Tierney CN, Norwick L, Hogarth DK, McConville JF, Naureckas ET, Sperling AI, Solway J, Krishnan JA, Nicolae DL, White SR, Ober C. Maternal asthma and microRNA regulation of soluble HLA-G in the airway. J Allergy Clin Immunol. 2013 Jun; 131(6):1496-503. View in: PubMed

  44. Patterson KC, Franek BS, Müller-Quernheim J, Sperling AI, Sweiss NJ, Niewold TB. Circulating cytokines in sarcoidosis: phenotype-specific alterations for fibrotic and non-fibrotic pulmonary disease. Cytokine. 2013 Mar; 61(3):906-11. View in: PubMed

  45. Shilling RA, Williams JW, Perera J, Berry E, Wu Q, Cummings OW, Sperling AI, Huang H. Autoreactive T and B cells induce the development of bronchus-associated lymphoid tissue in the lung. Am J Respir Cell Mol Biol. 2013 Apr; 48(4):406-14. View in: PubMed

  46. Williams JW, Tjota MY, Sperling AI. The contribution of allergen-specific IgG to the development of th2-mediated airway inflammation. J Allergy (Cairo). 2012; 2012:236075. View in: PubMed

  47. Patterson KC, Hogarth K, Husain AN, Sperling AI, Niewold TB. The clinical and immunologic features of pulmonary fibrosis in sarcoidosis. Transl Res. 2012 Nov; 160(5):321-31. View in: PubMed

  48. Edelblum KL, Shen L, Weber CR, Marchiando AM, Clay BS, Wang Y, Prinz I, Malissen B, Sperling AI, Turner JR. Dynamic migration of ?d intraepithelial lymphocytes requires occludin. Proc Natl Acad Sci U S A. 2012 May 01; 109(18):7097-102. View in: PubMed

  49. Zloza A, Kohlhapp FJ, Lyons GE, Schenkel JM, Moore TV, Lacek AT, O'Sullivan JA, Varanasi V, Williams JW, Jagoda MC, Bellavance EC, Marzo AL, Thomas PG, Zafirova B, Polic B, Al-Harthi L, Sperling AI, Guevara-Patiño JA. NKG2D signaling on CD8? T cells represses T-bet and rescues CD4-unhelped CD8? T cell memory recall but not effector responses. Nat Med. 2012 Feb 26; 18(3):422-8. View in: PubMed

  50. Moore TV, Clay BS, Cannon JL, Histed A, Shilling RA, Sperling AI. Inducible costimulator controls migration of T cells to the lungs via down-regulation of CCR7 and CD62L. Am J Respir Cell Mol Biol. 2011 Oct; 45(4):843-50. View in: PubMed

  51. Moore TV, Clay BS, Ferreira CM, Williams JW, Rogozinska M, Cannon JL, Shilling RA, Marzo AL, Sperling AI. Protective effector memory CD4 T cells depend on ICOS for survival. PLoS One. 2011 Feb 18; 6(2):e16529. View in: PubMed

  52. Cannon JL, Mody PD, Blaine KM, Chen EJ, Nelson AD, Sayles LJ, Moore TV, Clay BS, Dulin NO, Shilling RA, Burkhardt JK, Sperling AI. CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell trafficking and CD43 phosphorylation. Mol Biol Cell. 2011 Apr; 22(7):954-63. View in: PubMed

  53. Shaffer MH, Huang Y, Corbo E, Wu GF, Velez M, Choi JK, Saotome I, Cannon JL, McClatchey AI, Sperling AI, Maltzman JS, Oliver PM, Bhandoola A, Laufer TM, Burkhardt JK. Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice. PLoS One. 2010 Aug 27; 5(8):e12404. View in: PubMed

  54. Bhorade SM, Chen H, Molinero L, Liao C, Garrity ER, Vigneswaran WT, Shilling R, Sperling A, Chong A, Alegre ML. Decreased percentage of CD4+FoxP3+ cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome. Transplantation. 2010 Sep 15; 90(5):540-6. View in: PubMed

  55. Clay BS, Sperling AI. T-cell costimulation blockade in immunologic diseases: role of CD28 family members. Expert Rev Clin Immunol. 2007 May; 3(3):383-93. View in: PubMed

  56. Zhao Y, Tong J, He D, Pendyala S, Evgeny B, Chun J, Sperling AI, Natarajan V. Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma. Respir Res. 2009 Nov 20; 10:114. View in: PubMed

  57. Clay BS, Shilling RA, Bandukwala HS, Moore TV, Cannon JL, Welcher AA, Weinstock JV, Sperling AI. Inducible costimulator expression regulates the magnitude of Th2-mediated airway inflammation by regulating the number of Th2 cells. PLoS One. 2009 Nov 04; 4(11):e7525. View in: PubMed

  58. Tong J, Clay BS, Ferreira CM, Bandukwala HS, Moore TV, Blaine KM, Williams JW, Hoffman LM, Hamann KJ, Shilling RA, Weinstock JV, Sperling AI. Fas ligand expression on T cells is sufficient to prevent prolonged airway inflammation in a murine model of asthma. Am J Respir Cell Mol Biol. 2010 Sep; 43(3):342-8. View in: PubMed

  59. Shilling RA, Clay BS, Tesciuba AG, Berry EL, Lu T, Moore TV, Bandukwala HS, Tong J, Weinstock JV, Flavell RA, Horan T, Yoshinaga SK, Welcher AA, Cannon JL, Sperling AI. CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo. Cell Immunol. 2009; 259(2):177-84. View in: PubMed

  60. Tesciuba AG, Shilling RA, Agarwal MD, Bandukwala HS, Clay BS, Moore TV, Weinstock JV, Welcher AA, Sperling AI. ICOS costimulation expands Th2 immunity by augmenting migration of lymphocytes to draining lymph nodes. J Immunol. 2008 Jul 15; 181(2):1019-24. View in: PubMed

  61. Cannon JL, Collins A, Mody PD, Balachandran D, Henriksen KJ, Smith CE, Tong J, Clay BS, Miller SD, Sperling AI. CD43 regulates Th2 differentiation and inflammation. J Immunol. 2008 Jun 01; 180(11):7385-93. View in: PubMed

  62. Yau DM, Sethakorn N, Taurin S, Kregel S, Sandbo N, Camoretti-Mercado B, Sperling AI, Dulin NO. Regulation of Smad-mediated gene transcription by RGS3. Mol Pharmacol. 2008 May; 73(5):1356-61. View in: PubMed

  63. Pinto LH, Eaton E, Chen B, Fleisher J, Shuster D, McCauley J, Kedainis D, Siepka SM, Shimomura K, Song EJ, Husain A, Lakser OJ, Mitchell RW, Dowell ML, Brown M, Camoretti-Mercado B, Naclerio R, Sperling AI, Levin SI, Turek FW, Solway J. Gene-environment interactions in a mutant mouse kindred with native airway constrictor hyperresponsiveness. Mamm Genome. 2008 Jan; 19(1):2-14. View in: PubMed

  64. Bandukwala HS, Clay BS, Tong J, Mody PD, Cannon JL, Shilling RA, Verbeek JS, Weinstock JV, Solway J, Sperling AI. Signaling through Fc gamma RIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation. J Exp Med. 2007 Aug 06; 204(8):1875-89. View in: PubMed

  65. Mody PD, Cannon JL, Bandukwala HS, Blaine KM, Schilling AB, Swier K, Sperling AI. Signaling through CD43 regulates CD4 T-cell trafficking. Blood. 2007 Oct 15; 110(8):2974-82. View in: PubMed

  66. Shilling RA, Bandukwala HS, Sperling AI. Regulation of T:B cell interactions by the inducible costimulator molecule: does ICOS "induce" disease? Clin Immunol. 2006 Oct; 121(1):13-8. View in: PubMed

  67. Tong J, Bandulwala HS, Clay BS, Anders RA, Shilling RA, Balachandran DD, Chen B, Weinstock JV, Solway J, Hamann KJ, Sperling AI. Fas-positive T cells regulate the resolution of airway inflammation in a murine model of asthma. J Exp Med. 2006 May 15; 203(5):1173-84. View in: PubMed

  68. Blair C, Naclerio RM, Yu X, Thompson K, Sperling A. Role of type 1 T helper cells in the resolution of acute Streptococcus pneumoniae sinusitis: a mouse model. J Infect Dis. 2005 Oct 01; 192(7):1237-44. View in: PubMed

  69. Shilling RA, Pinto JM, Decker DC, Schneider DH, Bandukwala HS, Schneider JR, Camoretti-Mercado B, Ober C, Sperling AI. Cutting edge: polymorphisms in the ICOS promoter region are associated with allergic sensitization and Th2 cytokine production. J Immunol. 2005 Aug 15; 175(4):2061-5. View in: PubMed

  70. Sperling AI, Bluestone JA. Non-classical MHC molecules: the first line of defence? Curr Biol. 1993 May 01; 3(5):294-6. View in: PubMed

  71. Yu X, Sperling A, Blair C, Thompson K, Naclerio R. Antigen stimulation of TH2 cells augments acute bacterial sinusitis in mice. J Allergy Clin Immunol. 2004 Aug; 114(2):328-34. View in: PubMed

  72. Tong J, Allenspach EJ, Takahashi SM, Mody PD, Park C, Burkhardt JK, Sperling AI. CD43 regulation of T cell activation is not through steric inhibition of T cell-APC interactions but through an intracellular mechanism. J Exp Med. 2004 May 03; 199(9):1277-83. View in: PubMed

  73. Ford ML, Onami TM, Sperling AI, Ahmed R, Evavold BD. CD43 modulates severity and onset of experimental autoimmune encephalomyelitis. J Immunol. 2003 Dec 15; 171(12):6527-33. View in: PubMed

  74. Kang HS, Blink SE, Chin RK, Lee Y, Kim O, Weinstock J, Waldschmidt T, Conrad D, Chen B, Solway J, Sperling AI, Fu YX. Lymphotoxin is required for maintaining physiological levels of serum IgE that minimizes Th1-mediated airway inflammation. J Exp Med. 2003 Dec 01; 198(11):1643-52. View in: PubMed

  75. Dorscheid DR, Low E, Conforti A, Shifrin S, Sperling AI, White SR. Corticosteroid-induced apoptosis in mouse airway epithelium: effect in normal airways and after allergen-induced airway inflammation. J Allergy Clin Immunol. 2003 Feb; 111(2):360-6. View in: PubMed

  76. Cullinan P, Sperling AI, Burkhardt JK. The distal pole complex: a novel membrane domain distal to the immunological synapse. Immunol Rev. 2002 Nov; 189:111-22. View in: PubMed

  77. Muñoz NM, Boetticher E, Sperling AI, Kim KP, Meliton AY, Zhu X, Lambertino A, Cho W, Leff AR. Quantitation of secretory group V phospholipase A(2) in human tissues by sandwich enzyme-linked immunosorbent assay. J Immunol Methods. 2002 Apr 01; 262(1-2):41-51. View in: PubMed

  78. Allenspach EJ, Cullinan P, Tong J, Tang Q, Tesciuba AG, Cannon JL, Takahashi SM, Morgan R, Burkhardt JK, Sperling AI. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity. 2001 Nov; 15(5):739-50. View in: PubMed

  79. Sperling AI. ICOS costimulation: is it the key to selective immunotherapy? Clin Immunol. 2001 Sep; 100(3):261-2. View in: PubMed

  80. Tesciuba AG, Subudhi S, Rother RP, Faas SJ, Frantz AM, Elliot D, Weinstock J, Matis LA, Bluestone JA, Sperling AI. Inducible costimulator regulates Th2-mediated inflammation, but not Th2 differentiation, in a model of allergic airway disease. J Immunol. 2001 Aug 15; 167(4):1996-2003. View in: PubMed

  81. Sperling AI, Bluestone JA. ICOS costimulation: It's not just for TH2 cells anymore. Nat Immunol. 2001 Jul; 2(7):573-4. View in: PubMed

  82. Shiels H, Li X, Schumacker PT, Maltepe E, Padrid PA, Sperling A, Thompson CB, Lindsten T. TRAF4 deficiency leads to tracheal malformation with resulting alterations in air flow to the lungs. Am J Pathol. 2000 Aug; 157(2):679-88. View in: PubMed

  83. Muñoz NM, Kim KP, Han SK, Boetticher E, Sperling AI, Sano H, Zhu X, Cho W, Leff AR. Characterization of monoclonal antibodies specific for 14-kDa human group V secretory phospholipase A2 (hVPLA2). Hybridoma. 2000 Apr; 19(2):171-6. View in: PubMed

  84. Douglas IS, Leff AR, Sperling AI. CD4+ T cell and eosinophil adhesion is mediated by specific ICAM-3 ligation and results in eosinophil activation. J Immunol. 2000 Mar 15; 164(6):3385-91. View in: PubMed

  85. Rajagopal K, Sommers CL, Decker DC, Mitchell EO, Korthauer U, Sperling AI, Kozak CA, Love PE, Bluestone JA. RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation. J Exp Med. 1999 Dec 06; 190(11):1657-68. View in: PubMed

  86. Sperling AI, Sedy JR, Manjunath N, Kupfer A, Ardman B, Burkhardt JK. TCR signaling induces selective exclusion of CD43 from the T cell-antigen-presenting cell contact site. J Immunol. 1998 Dec 15; 161(12):6459-62. View in: PubMed

  87. Hamann KJ, Dorscheid DR, Ko FD, Conforti AE, Sperling AI, Rabe KF, White SR. Expression of Fas (CD95) and FasL (CD95L) in human airway epithelium. Am J Respir Cell Mol Biol. 1998 Oct; 19(4):537-42. View in: PubMed

  88. Padrid PA, Mathur M, Li X, Herrmann K, Qin Y, Cattamanchi A, Weinstock J, Elliott D, Sperling AI, Bluestone JA. CTLA4Ig inhibits airway eosinophilia and hyperresponsiveness by regulating the development of Th1/Th2 subsets in a murine model of asthma. Am J Respir Cell Mol Biol. 1998 Apr; 18(4):453-62. View in: PubMed

  89. Sperling AI, Decker DC, DiPaolo RJ, Stern DA, Shum A, Bluestone JA. Selective expansion of Vgamma2-Vdelta7 TCR gammadelta cells in C57BL/6 mice is postnatal and extrathymic. J Immunol. 1997 Jul 01; 159(1):86-91. View in: PubMed

  90. Sperling AI, Bluestone JA. The complexities of T-cell co-stimulation: CD28 and beyond. Immunol Rev. 1996 Oct; 153:155-82. View in: PubMed

  91. Rulifson IC, Sperling AI, Fields PE, Fitch FW, Bluestone JA. CD28 costimulation promotes the production of Th2 cytokines. J Immunol. 1997 Jan 15; 158(2):658-65. View in: PubMed

  92. Sperling AI, Auger JA, Ehst BD, Rulifson IC, Thompson CB, Bluestone JA. CD28/B7 interactions deliver a unique signal to naive T cells that regulates cell survival but not early proliferation. J Immunol. 1996 Nov 01; 157(9):3909-17. View in: PubMed

  93. Khattri R, Sperling AI, Qian D, Fitch FW, Shores EW, Love PE, Bluestone JA. TCR-gamma delta cells in CD3 zeta-deficient mice contain Fc epsilon RI gamma in the receptor complex but are specifically unresponsive to antigen. J Immunol. 1996 Sep 15; 157(6):2320-7. View in: PubMed

  94. Bluestone JA, Khattri R, Sciammas R, Sperling AI. TCR gamma delta cells: a specialized T-cell subset in the immune system. Annu Rev Cell Dev Biol. 1995; 11:307-53. View in: PubMed

  95. Green JM, Noel PJ, Sperling AI, Walunas TL, Lenschow DJ, Stack R, Gray GS, Bluestone JA, Thompson CB. T cell costimulation through the CD28 receptor. Proc Assoc Am Physicians. 1995 Apr; 107(1):41-6. View in: PubMed

  96. Walunas TL, Sperling AI, Khattri R, Thompson CB, Bluestone JA. CD28 expression is not essential for positive and negative selection of thymocytes or peripheral T cell tolerance. J Immunol. 1996 Feb 01; 156(3):1006-13. View in: PubMed

  97. Qian D, Sperling AI, Lancki DW, Tatsumi Y, Barrett TA, Bluestone JA, Fitch FW. The gamma chain of the high-affinity receptor for IgE is a major functional subunit of the T-cell antigen receptor complex in gamma delta T lymphocytes. Proc Natl Acad Sci U S A. 1993 Dec 15; 90(24):11875-9. View in: PubMed

  98. Peterman GM, Spencer C, Sperling AI, Bluestone JA. Role of gamma delta T cells in murine collagen-induced arthritis. J Immunol. 1993 Dec 01; 151(11):6546-58. View in: PubMed

  99. Sperling AI, Linsley PS, Barrett TA, Bluestone JA. CD28-mediated costimulation is necessary for the activation of T cell receptor-gamma delta+ T lymphocytes. J Immunol. 1993 Dec 01; 151(11):6043-50. View in: PubMed

  100. Sciammas R, Johnson RM, Sperling AI, Brady W, Linsley PS, Spear PG, Fitch FW, Bluestone JA. Unique antigen recognition by a herpesvirus-specific TCR-gamma delta cell. J Immunol. 1994 Jun 01; 152(11):5392-7. View in: PubMed

  101. Sperling AI, Green JM, Mosley RL, Smith PL, DiPaolo RJ, Klein JR, Bluestone JA, Thompson CB. CD43 is a murine T cell costimulatory receptor that functions independently of CD28. J Exp Med. 1995 Jul 01; 182(1):139-46. View in: PubMed

  102. Sciammas R, Tatsumi Y, Sperling AI, Arunan K, Bluestone JA. TCR gamma delta cells: mysterious cells of the immune system. Immunol Res. 1994; 13(4):268-79. View in: PubMed

  103. Sandor M, Sperling AI, Cook GA, Weinstock JV, Lynch RG, Bluestone JA. Two waves of gamma delta T cells expressing different V delta genes are recruited into schistosome-induced liver granulomas. J Immunol. 1995 Jul 01; 155(1):275-84. View in: PubMed

  104. Green JM, Noel PJ, Sperling AI, Walunas TL, Gray GS, Bluestone JA, Thompson CB. Absence of B7-dependent responses in CD28-deficient mice. Immunity. 1994 Sep; 1(6):501-8. View in: PubMed

  105. Lenschow DJ, Sperling AI, Cooke MP, Freeman G, Rhee L, Decker DC, Gray G, Nadler LM, Goodnow CC, Bluestone JA. Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig receptor engagement by antigen. J Immunol. 1994 Sep 01; 153(5):1990-7. View in: PubMed

  106. Sperling AI, Wortis HH. CD4-, CD8- gamma/delta cells from normal mice respond to a syngeneic B cell lymphoma and can induce its differentiation. Int Immunol. 1989; 1(4):434-42. View in: PubMed

  107. Bluestone JA, Cron RQ, Barrett TA, Houlden B, Sperling AI, Dent A, Hedrick S, Rellahan B, Matis LA. Repertoire development and ligand specificity of murine TCR gamma delta cells. Immunol Rev. 1991 Apr; 120:5-33. View in: PubMed

  108. Sperling AI, Cron RQ, Decker DC, Stern DA, Bluestone JA. Peripheral T cell receptor gamma delta variable gene repertoire maps to the T cell receptor loci and is influenced by positive selection. J Immunol. 1992 Nov 15; 149(10):3200-7. View in: PubMed

  109. Johnson RM, Lancki DW, Sperling AI, Dick RF, Spear PG, Fitch FW, Bluestone JA. A murine CD4-, CD8- T cell receptor-gamma delta T lymphocyte clone specific for herpes simplex virus glycoprotein I. J Immunol. 1992 Feb 15; 148(4):983-8. View in: PubMed