IL-22-dependent Dysbiosis and Mononuclear Phagocyte Depletion Contribute to Steroid-resistant Gut Graft-versus-host Disease in Mice

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Feb 6

PMID 33547295

Citations 11

Authors

Qingxiao Song

Xiaoning Wang

Xiwei Wu

Tae Hyuk Kang

Hanjun Qin

Dongchang Zhao

Robert R Jenq

Marcel R M van den Brink

Arthur D Riggs

Paul J Martin

Yuan-Zhong Chen

Defu Zeng

Affiliations

Soon will be listed here.

Abstract

Efforts to improve the prognosis of steroid-resistant gut acute graft-versus-host-disease (SR-Gut-aGVHD) have suffered from poor understanding of its pathogenesis. Here we show that the pathogenesis of SR-Gut-aGVHD is associated with reduction of IFN-γ Th/Tc1 cells and preferential expansion of IL-17IL-22 Th/Tc22 cells. The IL-22 from Th/Tc22 cells causes dysbiosis in a Reg3γ-dependent manner. Transplantation of IFN-γ-deficient donor CD8 T cells in the absence of CD4 T cells produces a phenocopy of SR-Gut-aGVHD. IFN-γ deficiency in donor CD8 T cells also leads to a PD-1-dependent depletion of intestinal protective CX3CR1 mononuclear phagocytes (MNP), which also augments expansion of Tc22 cells. Supporting the dual regulation, simultaneous dysbiosis induction and depletion of CX3CR1 MNP results in full-blown Gut-aGVHD. Our results thus provide insights into SR-Gut-aGVHD pathogenesis and suggest the potential efficacy of IL-22 antagonists and IFN-γ agonists in SR-Gut-aGVHD therapy.

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