Jane Buckner, M.D.

PRESIDENT AND MEMBER, BENAROYA RESEARCH INSTITUTE
DIRECTOR, TRANSLATIONAL RESEARCH PROGRAM
AFFILIATE PROFESSOR, DEPARTMENT OF IMMUNOLOGY

RESEARCH

Dr. Buckner’s research focuses on identifying the underlying mechanisms by which the adaptive immune response to self-antigens becomes pathogenic in the setting of human autoimmune disease. To this end, Dr. Buckner’s group studies how both regulatory and effector mechanisms are altered in autoimmunity.

The lab works on three areas of autoimmunity:

1. Antigen-specific T cells in rheumatoid arthritis. These studies are characterizing antigen-specific T cells in rheumatoid arthritis using tools that include multiplex tetramer approaches. The long-term goal of these studies is to understand the specificity of the pathogenic response in rheumatoid arthritis, and to determine how the frequency and phenotype of antigen-specific T cells is altered with respect to disease activity and response to therapy. The Buckner group is also assessing antigen-specific T cell responses with respect to T cell repertoire and transcriptional profile in both individuals with rheumatoid arthritis and in individuals at high risk for rheumatoid arthritis.
2. Regulatory T cell-based therapy for T1D and RA. In collaboration with Dr. David Rawlings at Seattle Children’s Hospital, the Buckner lab is using novel gene editing tools to engineered FOXP-3 stabilized, tissue-specific T cells. This work has focused on in vitro induction, isolation and expansion of human tissue-specific regulatory T cells.  Recently, they have also established methods to deliver islet-specific T cell receptors to target the engineered regulatory T cells to the pancreas.
3. The influence of genetic variants associated with autoimmune disease and alterations in cytokine signaling pathways on the development and progression of autoimmune disease. Dr. Buckner’s group has a long-standing interest in determining the functional impact of genetic variants associated with type 1 diabetes and lupus including PTPN22, IL2RA, PTPN2, BANK1, IFIH1 and TYK2. Their work has shown that the PTPN22 risk variant alters B cell signaling and B cell development, and their studies of both the IL2RA and the PTPN2 risk variants associated with T1D have demonstrated an association with reduced responsiveness to IL-2 signaling in regulatory T cells in type 1 diabetes and multiple sclerosis. The Buckner group’s work on IL-2 signaling highlights the importance of this pathway in the maintenance of FOXP3 expression in regulatory T cells in type 1 diabetes. Furthermore, recent work from the Buckner lab has shown that the T cell response to IL-6 signaling is enhanced in type 1 diabetes and relapsing-remitting multiple sclerosis. Ongoing studies are investigating how alterations in response to cytokine signaling influence the expansion and persistence of pathogenic autoreactive effector T cells. These studies examine the response to cytokine signaling in the context of clinical, genetic and immunologic heterogeneity of human subjects, which is critical for the development of precision medicine for the prevention and treatment of autoimmune disease.

PUBLICATIONS

1. Long SA, Cerosaletti K, Bollyky PL, Tatum M, Shilling H, Zhang S, Zhang ZY, Pihoker C, Sanda S, Greenbaum C, Buckner JH. Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects. Diabetes. 2010 Feb;59(2):407-15.
2. Hundhausen C, Roth A, Whalen E, Chen J, Schneider A, Long SA, Wei S, Rawlings R, Kinsman M, Evanko SP, Wight TN, Greenbaum CJ, Cerosaletti K, Buckner JH. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci Transl Med. 2016 Sep 14;8(356):356ra119.
3. Schneider A, Long SA, Cerosaletti K, Ni CT, Samuels P, Kita M, Buckner JH. In active relapsing-remitting multiple sclerosis, effector T cell resistance to adaptive T(regs) involves IL-6-mediated signaling. Sci Transl Med. 2013 Jan 30;5(170):170ra15.
4. James EA, Rieck M, Pieper J, Gebe JA, Yue BB, Tatum M, Peda M, Sandin C, Klareskog L, Malmström V, Buckner JH. Citrulline-specific Th1 cells are increased in rheumatoid arthritis and their frequency is influenced by disease duration and therapy. Arthritis Rheumatol. 2014 Jul;66(7):1712-22.
5. Habib T, Long SA, Samuels PL, Brahmandam A, Tatum M, Funk A, Hocking AM, Cerosaletti K, Mason MT, Whalen E, Rawlings DJ, Greenbaum C, Buckner JH; Type 1 Diabetes TrialNet Study Group. Dynamic immune phenotypes of B and T helper cells mark distinct stages of T1D progression. Diabetes. 2019 Jun;68(6):1240-1250.
6. Gorman JA, Hundhausen C, Kinsman M, Arkatkar T, Allenspach EJ, Clough C, West SE, Thomas K, Eken A, Khim S, Hale M, Oukka M, Jackson SW, Cerosaletti K, Buckner JH, Rawlings DJ. The TYK2-P1104A autoimmune protective variant limits coordinate signals required to generate specialized T cell subsets. Front Immunol. 2019 Jan 25;10:44.
7. Bolouri H, Speake C, Skibinski D, Long SA, Hocking AM, Campbell DJ, Hamerman JA, Malhotra U, Buckner JH; Benaroya Research Institute COVID-19 Research Team. The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity. J Clin Invest. 2021 Feb 1;131(3):e143648.
8. Song J, Schwenzer A, Wong A, Turcinov S, Rims C, Martinez LR, Arribas-Layton D, Gerstner C, Muir VS, Midwood KS, Malmström V, James EA, Buckner JH. Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis. JCI Insight. 2021 Mar 8;6(5):e145217.
9. Honaker Y, Hubbard N, Xiang Y, Fisher L, Hagin D, Sommer K, Song Y, Yang SJ, Lopez C, Tappen T, Dam EM, Khan I, Hale M, Buckner JH, Scharenberg AM, Torgerson TR, Rawlings DJ. Gene editing to induce FOXP3 expression in human CD4⁺ T cells leads to a stable regulatory phenotype and function. Sci Transl Med. 2020 Jun 3;12(546):eaay6422.
10. Gorman JA, Hundhausen C, Errett JS, Stone AE, Allenspach EJ, Ge Y, Arkatkar T, Clough C, Dai X, Khim S, Pestal K, Liggitt D, Cerosaletti K, Stetson DB, James RG, Oukka M, Concannon P, Gale M Jr, Buckner JH, Rawlings DJ. The A946T variant of the RNA sensor IFIH1 mediates an interferon program that limits viral infection but increases the risk for autoimmunity. Nat Immunol. 2017 Jul;18(7):744-752.
11. Bluestone JA, Buckner JH, Herold KC. Immunotherapy: Building a bridge to a cure for type 1 diabetes. Science. 2021 Jul 30;373(6554):510-516.

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