IL-22 is required for the induction of bronchus-associated lymphoid tissue in tolerant lung allografts.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2020 May

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Long-term survival after lung transplantation remains profoundly limited by graft rejection. Recent work has shown that bronchus-associated lymphoid tissue (BALT), characterized by the development of peripheral nodal addressin (PNAd)-expressing high endothelial venules and enriched in B and Foxp3+ T cells, is important for the maintenance of allograft tolerance. Mechanisms underlying BALT induction in tolerant pulmonary allografts, however, remain poorly understood. Here, we show that the development of PNAd-expressing high endothelial venules within intragraft lymphoid follicles and the recruitment of B cells, but not Foxp3+ cells depends on IL-22. We identify graft-infiltrating gamma-delta (γδ) T cells and Type 3 innate lymphoid cells (ILC3s) as important producers of IL-22. Reconstitution of IL-22 at late time points through retransplantation into wildtype hosts mediates B cell recruitment into lymphoid follicles within the allograft, resulting in a significant increase in their size, but does not induce PNAd expression. Our work has identified cellular and molecular requirements for the induction of BALT in pulmonary allografts during tolerance induction and may provide a platform for the development of new therapies for lung transplant patients. © 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.

Citation

Satona Tanaka, Jason M Gauthier, Anja Fuchs, Wenjun Li, Alice Y Tong, Margaret S Harrison, Ryuji Higashikubo, Yuriko Terada, Ramsey R Hachem, Daniel Ruiz-Perez, Jon H Ritter, Marina Cella, Marco Colonna, Isaiah R Turnbull, Alexander S Krupnick, Andrew E Gelman, Daniel Kreisel. IL-22 is required for the induction of bronchus-associated lymphoid tissue in tolerant lung allografts. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020 May;20(5):1251-1261