A nonredundant role for T cell-derived interleukin 22 in antibacterial defense of colonic crypts

Carlene L Zindl; Steven J Witte; Vincent A Laufer; Min Gao; Zongliang Yue; Karen M Janowski; Baiyi Cai; Blake F Frey; Daniel J Silberger; Stacey N Harbour; Jeffrey R Singer; Henrietta Turner; Frances E Lund; Bruce A Vallance; Alexander F Rosenberg; Trenton R Schoeb; Jake Y Chen; Robin D Hatton; Casey T Weaver

doi:10.1016/j.immuni.2022.02.003

A nonredundant role for T cell-derived interleukin 22 in antibacterial defense of colonic crypts

Immunity. 2022 Mar 8;55(3):494-511.e11. doi: 10.1016/j.immuni.2022.02.003.

Authors

Carlene L Zindl¹, Steven J Witte², Vincent A Laufer², Min Gao³, Zongliang Yue³, Karen M Janowski⁴, Baiyi Cai⁵, Blake F Frey⁵, Daniel J Silberger⁵, Stacey N Harbour⁵, Jeffrey R Singer⁵, Henrietta Turner⁵, Frances E Lund⁶, Bruce A Vallance⁷, Alexander F Rosenberg⁸, Trenton R Schoeb⁴, Jake Y Chen³, Robin D Hatton⁵, Casey T Weaver⁹

Affiliations

¹ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: carlenezindl@uabmc.edu.
² Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
³ Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Informatics Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁴ Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁵ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁶ Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁷ Department of Pediatrics, University of British Columbia, Vancouver, BC V6H 3V4, Canada.
⁸ Informatics Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁹ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: cweaver@uab.edu.

Abstract

Interleukin (IL)-22 is central to immune defense at barrier sites. We examined the contributions of innate lymphoid cell (ILC) and T cell-derived IL-22 during Citrobacter rodentium (C.r) infection using mice that both report Il22 expression and allow lineage-specific deletion. ILC-derived IL-22 activated STAT3 in C.r-colonized surface intestinal epithelial cells (IECs) but only temporally restrained bacterial growth. T cell-derived IL-22 induced a more robust and extensive activation of STAT3 in IECs, including IECs lining colonic crypts, and T cell-specific deficiency of IL-22 led to pathogen invasion of the crypts and increased mortality. This reflected a requirement for T cell-derived IL-22 for the expression of a host-protective transcriptomic program that included AMPs, neutrophil-recruiting chemokines, and mucin-related molecules, and it restricted IFNγ-induced proinflammatory genes. Our findings demonstrate spatiotemporal differences in the production and action of IL-22 by ILCs and T cells during infection and reveal an indispensable role for IL-22-producing T cells in the protection of the intestinal crypts.

Keywords: AMPs; CD4 T cells; Citrobacter rodentium; IFNγ; IL-22; TNF; chemokines; colonic crypt IECs; colonic surface IECs; innate cells; mucins.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Anti-Bacterial Agents
Citrobacter rodentium*
Enterobacteriaceae Infections*
Immunity, Innate
Interleukin-22
Interleukins / metabolism
Intestinal Mucosa
Lymphocytes / metabolism
Mice
Mice, Inbred C57BL
T-Lymphocytes / metabolism

Substances

Anti-Bacterial Agents
Interleukins

Abstract

Publication types

MeSH terms

Substances

Grants and funding