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Interleukin-22 accelerates thymus regeneration via Stat3/Mcl-1 and decreases chronic graft-versus-host disease in mice after allotransplants.

08:00 EDT 10th June 2019 | BioPortfolio

Summary of "Interleukin-22 accelerates thymus regeneration via Stat3/Mcl-1 and decreases chronic graft-versus-host disease in mice after allotransplants."

High-dose chemotherapy and/or radiation given before an allogeneic hematopoietic cell transplantation severely damage thymic epithelial cells (TECs) resulting in poor posttransplant immune recovery. IL-22 mediates recovery of TECs via a pro-regenerative effect but the precise mechanism by which this occurs is unknown. In this study, we found IL-22 improved thymus recovery after damage from irradiation in association with increased number of TECs. This effect was blocked by ruxolitinib, a JAK1/JAK2-inhibitor. IL-22 increased the number of TECs via a Stat3-dependent signaling in the mTEC1 murine thymic epithelial cell line. This, in turn, upregulated transcription of myeloid cell leukemia sequence 1 (Mcl1) resulting in increased number of TECs. Similar effects were seen in irradiated mice given IL-22. Defects in IL-22 resulted in delayed thymus recovery in irradiated mice and had an impact on levels of thymus function related genes such as Foxn1, Aire and Kgf. In mice, posttransplant use of IL-22 improved repair of TECs, increased the numbers of thymus T cells, increased the intra-thymic levels of Aire and increased proportion of natural regulatory T cells resulting in decreased severity of chronic graft-versus-host disease (GVHD). Our data highlight the critical role of the IL-22/Stat3/Mcl-1 pathway in regeneration of TECs after damage from irradiation in mice and highlight circumstances where normalizing thymus T-cell function with IL-22 decreases GVHD post allotransplants.

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This article was published in the following journal.

Name: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
ISSN: 1523-6536
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