Tonic Interferon Restricts Pathogenic IL-17-driven Inflammatory Disease Via Balancing the Microbiome

Overview

Journal Elife

Specialty Biology

Date 2021 Aug 11

PMID 34378531

Citations 18

Authors

Isabelle J Marie

Lara Brambilla

Doua Azzouz

Ze Chen

Gisele V Baracho

Azlann Arnett

Haiyan S Li

Weiguo Liu

Luisa Cimmino

Pratip Chattopadhyay

Gregg Silverman

Stephanie S Watowich

Bernard Khor

David E Levy

Affiliations

Soon will be listed here.

Abstract

Maintenance of immune homeostasis involves a synergistic relationship between the host and the microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement of the STAT1 transcription factor. However, the contribution of tonic levels of IFN to immune homeostasis in the absence of acute infection remains largely unexplored. We report that STAT1 KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia and splenic accumulation of hematopoietic stem cells. Moreover, these animals developed inflammatory bowel disease. Profiling gut bacteria revealed a profound dysbiosis in the absence of tonic IFN signaling, which triggered expansion of T17 cells and loss of splenic T cells. Reduction of bacterial load by antibiotic treatment averted the T17 bias and blocking IL17 signaling prevented myeloid expansion and splenic stem cell accumulation. Thus, tonic IFNs regulate gut microbial ecology, which is crucial for maintaining physiologic immune homeostasis and preventing inflammation.

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