Anne I. Sperling

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Primary Appointment

Professor, Medicine- Pulmonary and Critical Care Medicine

Education

  • AB, Biology, Smith College
  • PhD, Immunology, Tufts University, Boston, MA

Research Disciplines

Biology, Experimental Pathology, Immunology, Neuroimmunology, Translational Science

Research Interests

Immune Responses in asthma, pulmonary fibrosis, and lung injury.

Research Description

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.

Personal Statement

Dr. Sperling is a Professor of Medicine and Vice-Chair for Research in the Pulmonary and Critical Care Division with joint appointments in the Department of Microbiology, Immunology, and Cancer as well as the Carter Immunology Center. She is the Director of the Immunology Training Program and for the Interdisciplinary Training in Immunology T32 grant. Dr. Sperling joined the faculty at the University of Virginia in September 2021, following 25 years at the University of Chicago, where she advanced through the ranks from Instructor to Full Professor with tenure. Her past and current trainees include 17 MD or PhD post-doctoral fellows and 16 graduate students, including 2 MSTPs. Of the past trainees, 13 have remained in academia, 3 are scientists in industry, 3 are involved in medical or scientific writing, and 1 is teaching science in schools. Dr. Sperling has been continuously NIH-funded since 1999.
The Sperling Lab's mission is to:
1) advance understanding of immune responses involved in asthma and pulmonary fibrosis.
2) nurture the next generation of scientists and physician-scientists by actively engaging them in every phase of the research process.
3) create a collaborative and supportive environment that fosters scientific discovery, learning, and professional growth.

Selected Publications

Selected from >124 total peer-reviewed orginal publications.

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