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IL‐22 is required for the induction of bronchus‐associated lymphoid tissue in tolerant lung allografts
Author(s) -
Tanaka Satona,
Gauthier Jason M.,
Fuchs Anja,
Li Wenjun,
Tong Alice Y.,
Harrison Margaret S.,
Higashikubo Ryuji,
Terada Yuriko,
Hachem Ramsey R.,
RuizPerez Daniel,
Ritter Jon H.,
Cella Marina,
Colonna Marco,
Turnbull Isaiah R.,
Krupnick Alexander S.,
Gelman Andrew E.,
Kreisel Daniel
Publication year - 2020
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15701
Subject(s) - addressin , foxp3 , immunology , lung , lymphatic system , high endothelial venules , lung transplantation , medicine , transplantation , immune tolerance , biology , immune system , cell , cell adhesion , genetics
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.