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

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1251-1261
Number of pages11
JournalAmerican Journal of Transplantation
Volume20
Issue number5
DOIs
StatePublished - May 1 2020

Keywords

  • animal models: murine
  • basic (laboratory) research/science
  • immunobiology
  • lung transplantation/pulmonology
  • lymph node
  • lymphocyte biology
  • tolerance: experimental

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