Anne I. Sperling, PhD
PRIMARY APPOINTMENT:
Professor, Department of Medicine, Division of Pulmonary and Critical Care
CONTACT:
UVA Division of Pulmonary and Critical Care
PO Box 800546
Charlottesville, VA 22908
Telephone: 434-243-2706
Fax: 434-924-9682
Email: EMH5PG@virginia.edu
EDUCATION AND TRAINING:
- AB, Biology, Smith College
- PhD, Immunology, Tufts University, Boston, MA
RESEARCH
The Sperling lab focuses on the role of the immune system in the development and progression of lung disease. In mouse models, we have made significant contributions to our understanding of how T cell costimulatory molecules influence inflammation and disease, the role of lung dendritic cells in initiating type 2 inflammatory responses, and the regulation of inflammation resolution in allergic asthma. Our human translational studies have investigated how genetically regulated costimulatory molecule expression influences atopy, how asthma-protective environments impact immune profiles and function in farm children, and how immune cells in the blood, lymph nodes, and lungs of patients with progressive pulmonary fibrosis impact disease progression. Our studies have been published in numerous high-impact journals, including the New England Journal of Medicine, American Journal of Respiratory and Critical Care Medicine, Immunity, Journal of Clinical Investigation, Journal of Experimental Medicine, Nature Communications, Blood, JACI, and Mucosal Immunology.
Immune Responses in asthma, pulmonary fibrosis, and lung injury
Velez* TE, Yoon* YM, Upadhyay* V, Vazquez SE, Lee CT, . . . Shum^ AK, Sperling^ AI. Active Antigen-Specific Adaptive Immune Responses Are Shared among Patients with Progressive Fibrotic Interstitial Lung Disease. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2025 Aug 15. doi: 10.1164/rccm.202502-0419OC. Epub ahead of print. PMID: 40815686. *^These authors contributed equally to these studies
Wei X, Qian W, Narasimhan H, Chan T, Liu X, Arish M, Young S, Li C, Cheon IS, Yu Q, Almeida-Santos G, Zhao XY, Yeatts EV, Spear OJ, Yi M, Parimon T, Fang Y, Hahn YS, Bullock TNJ, Somerville LA, Kaplan MH, Sperling AI, . . . Sun J. Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae. SCIENCE. 2025 Mar 7;387(6738):eadq2509. doi: 10.1126/science.adq2509. Epub 2025 Mar 7. PMID: 40048515.
Zhao AY, Unterman A, Abu Hussein NS, Sharma P, Nekola F, Flint J, Yan X, Adams TS, Justet A, Sumida TS, Zhao J, Schupp JC, Raredon MSB, Ahangari F, Deluliis G, Zhang Y, Buendia-Roldan I, Adegunsoye A, Sperling AI, . . . Kaminski N. Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2024 Jun 26. doi: 10.1164/rccm.202401-0078OC. Epub ahead of print. PMID: 3892477
Upadhyay V, Yoon YM, Vazquez SE, Velez TE, . . . *Sperling AI, *Shum AK. Phage Immunoprecipitation-Sequencing Reveals CDHR5 Autoantibodies in Select Patients With Interstitial Lung Disease. ACR Open Rheumatol. 2024 Jul 1. doi: 10.1002/acr2.11696. Epub ahead of print. PMID: 38952015. *Co-Senior
Kalinina, O., Minter, L. M., Sperling, A. I., Hollinger, M. K., Le, P., Osborne, B. A., . . . Knight, K. L. (2024). Exopolysaccharide-Treated Dendritic Cells Effectively Ameliorate Acute Graft-versus-Host Disease.. Transplantation and cellular therapy, 30(1), 79.e1-79.e10. doi:10.1016/j.jtct.2023.10.023
Camacho, D. F., Velez, T. E., Hollinger, M. K., Wang, E., Howard, C. L., Darnell, E. P., . . . Sperling, A. I. (2022). IRF4 expression by lung dendritic cells drives acute but not Trm cell-dependent memory Th2 responses. JCI INSIGHT, 7(21). doi:10.1172/jci.insight.140384
Aneas, I., Decker, D. C., Howard, C. L., Sobreira, D. R., Sakabe, N. J., Blaine, K. M., . . . Nobrega, M. A. (2021). Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region. NATURE COMMUNICATIONS, 12(1). doi:10.1038/s41467-021-26347-z
Barnes, H., Troy, L., Lee, C. T., Sperling, A., Strek, M., & Glaspole, I. (2022). Hypersensitivity pneumonitis: Current concepts in pathogenesis, diagnosis, and treatment. ALLERGY, 77(2), 442-453. doi:10.1111/all.15017
Krishack, P. A., Hollinger, M. K., Kuzel, T. G., Decker, T. S., Louviere, T. J., Hrusch, C. L., . . . Verhoef, P. A. (2021). IL-33-mediated Eosinophilia Protects against Acute Lung Injury. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 64(5), 569-578. doi:10.1165/rcmb.2020-0166OC
Si, Y., Tian, Q., Zhao, F., Kelly, S. H., Shores, L. S., Camacho, D. F., . . .Sperling, A. I., Chong, A. S. (2020). Adjuvant-free nanofiber vaccine induces in situ lung dendritic cell activation and TH17 responses. SCIENCE ADVANCES, 6(32). doi:10.1126/sciadv.aba0995
Maisel, K., Hrusch, C. L., Medellin, J. E. G., Potin, L., Chapel, D. B., Nurmi, H., . . . , Sperling, A. I., Swartz, M. A. (2021). Pro-lymphangiogenic VEGFR-3 signaling modulates memory T cell responses in allergic airway inflammation. MUCOSAL IMMUNOLOGY, 14(1), 144-151. doi:10.1038/s41385-020-0308-4
Hrusch, C. L., Stein, M. M., Gozdz, J., Holbreich, M., von Mutius, E., Vercelli, D., . . . Sperling, A. I. (2019). T-cell phenotypes are associated with serum IgE levels in Amish and Hutterite children. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 144(5), 1391-+. doi:10.1016/j.jaci.2019.07.034
Krishack, P. A., Louviere, T. J., Decker, T. S., Kuzel, T. G., Greenberg, J. A., Camacho, D. F., . . . Verhoef, P. A. (2019). Protection against Staphylococcus aureus bacteremia-induced mortality depends on ILC2s and eosinophils. JCI INSIGHT, 4(6). doi:10.1172/jci.insight.124168
Adegunsoye, A., Oldham, J. M., Bonham, C., Hrusch, C., Nolan, P., Klejch, W., . . . Chung, J. H. (2019). Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment An Observational Cohort Study with Independent Validation. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 199(6), 747-759. doi:10.1164/rccm.201804-0761OC
Schoettler, N., Hrusch, C. L., Blaine, K. M., Sperling, A. I., & Ober, C. (2019). Transcriptional programming and T cell receptor repertoires distinguish human lung and lymph node memory T cells. COMMUNICATIONS BIOLOGY, 2. doi:10.1038/s42003-019-0657-2
Bonham, C. A., Hrusch, C. L., Blaine, K. M., Manns, S. T., Vij, R., Oldham, J. M., . . . Sperling, A. I. (2019). T cell Co-Stimulatory molecules ICOS and CD28 stratify idiopathic pulmonary fibrosis survival.. Respiratory medicine: X, 1, 100002. doi:10.1016/j.yrmex.2019.100002
Stein, M. M., Hrusch, C. L., Sperling, A. I., & Ober, C. (2019). Effects of an FcγRIIA polymorphism on leukocyte gene expression and cytokine responses to anti-CD3 and anti-CD28 antibodies. GENES AND IMMUNITY, 20(6), 462-472. doi:10.1038/s41435-018-0038-8
Ferreira, C. M., Williams, J. W., Tong, J., Rayon, C., Blaine, K. M., & Sperling, A. I. (2018). Allergen Exposure in Lymphopenic Fas-Deficient Mice Results in Persistent Eosinophilia Due to Defects in Resolution of Inflammation. FRONTIERS IN IMMUNOLOGY, 9. doi:10.3389/fimmu.2018.02395
Williams, J. W., Ferreira, C. M., Blaine, K. M., Rayon, C., Velazquez, F., Tong, J., . . . Sperling, A. I. (2018). Non-apoptotic Fas (CD95) Signaling on T Cells Regulates the Resolution of Th2-Mediated Inflammation. FRONTIERS IN IMMUNOLOGY, 9. doi:10.3389/fimmu.2018.02521
Krishack, P. A., Wang, K., Rzhetsky, A., Solway, J., Sperling, A. I., & Verhoef, P. A. (2017). Preexisting Type 2 Immune Activation Protects against the Development of Sepsis. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 57(5), 628-630. doi:10.1165/rcmb.2017-0277LE
Ober, C., Sperling, A. I., von Mutius, E., & Vercelli, D. (2017). Immune development and environment: lessons from Amish and Hutterite children. CURRENT OPINION IN IMMUNOLOGY, 48, 51-60. doi:10.1016/j.coi.2017.08.003
Hrusch, C. L., Manns, S. T., Bryazka, D., Casaos, J., Bonham, C. A., Jaffery, M. R., . . . Sperling, A. I. (2018). ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s. MUCOSAL IMMUNOLOGY, 11(1), 61-70. doi:10.1038/mi.2017.42
Stein, M. M., Hrusch, C. L., Gozdz, J., Igartua, C., Pivniouk, V., Murray, S. E., . . . Sperling, A. I. (2016). Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. NEW ENGLAND JOURNAL OF MEDICINE, 375(5), 411-421. doi:10.1056/NEJMoa1508749
Adegunsoye, A., Hrusch, C. L., Bonham, C. A., Jaffrey, M. R., Blaine, K. M., Sullivan, M., . . . Sperling, A. I. (2016). Skewed Lung CCR4 to CCR6 CD4+ T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function. FRONTIERS IN IMMUNOLOGY, 7. doi:10.3389/fimmu.2016.00516
Verhoef, P. A., Constantinides, M. G., McDonald, B. D., Urban, J. F. J., Sperling, A. I., & Bendelac, A. (2016). Intrinsic functional defects of type 2 innate lymphoid cells impair innate allergic inflammation in promyelocytic leukemia zinc finger (PLZF)-deficient mice. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 137(2), 591-+. doi:10.1016/j.jaci.2015.07.050
Sperling, A. I., & Ansel, K. M. (2014). Editorial overview: Allergy and hypersensitivity. CURRENT OPINION IN IMMUNOLOGY, 31, IX-XI. doi:10.1016/j.coi.2014.10.011
Hrusch, C. L., Tjota, M. Y., & Sperling, A. I. (2015). The Role of Dendritic Cells and Monocytes in the Maintenance and Loss of Respiratory Tolerance. CURRENT ALLERGY AND ASTHMA REPORTS, 15(1). doi:10.1007/s11882-014-0494-9
Tjota, M. Y., & Sperling, A. I. (2014). Distinct dendritic cell subsets actively induce Th2 polarization. CURRENT OPINION IN IMMUNOLOGY, 31, 44-50. doi:10.1016/j.coi.2014.09.006
Tjota, M. Y., Hrusch, C. L., Blaine, K. M., Williams, J. W., Barrett, N. A., & Sperling, A. I. (2014). Signaling through FcRγ-associated receptors on dendritic cells drives IL-33-dependent TH2-type responses. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 134(3), 706-+. doi:10.1016/j.jaci.2014.06.013
Tjota, M. Y., Williams, J. W., Lu, T., Clay, B. S., Byrd, T., Hrusch, C. L., . . . Sperling, A. I. (2013). IL-33-dependent induction of allergic lung inflammation by FcγRIII signaling. JOURNAL OF CLINICAL INVESTIGATION, 123(5), 2287-2297. doi:10.1172/JCI63802
Williams, J. W., Tjota, M. Y., Clay, B. S., Lugt, B. V., Bandukwala, H. S., Hrusch, C. L., . . . Sperling, A. I. (2013). Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation. NATURE COMMUNICATIONS, 4. doi:10.1038/ncomms3990