IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake

The Journal of Experimental Medicine
Toshi JinnoharaHiroshi Ohno

Abstract

Interleukin-22 (IL-22) acts protectively and harmfully on intestinal tissue depending on the situation; therefore, IL-22 signaling needs to be tightly regulated. IL-22 binding protein (IL-22BP) binds IL-22 to inhibit IL-22 signaling. It is expressed in intestinal and lymphoid tissues, although its precise distribution and roles have remained unclear. In this study, we show that IL-22BP is highly expressed by CD11b+CD8α- dendritic cells in the subepithelial dome region of Peyer's patches (PPs). We found that IL-22BP blocks IL-22 signaling in the follicle-associated epithelium (FAE) covering PPs, indicating that IL-22BP plays a role in regulating the characteristics of the FAE. As expected, FAE of IL-22BP-deficient (Il22ra2-/-) mice exhibited altered properties such as the enhanced expression of mucus and antimicrobial proteins as well as prominent fucosylation, which are normally suppressed in FAE. Additionally, Il22ra2-/- mice exhibited the decreased uptake of bacterial antigens into PPs without affecting M cell function. Our present study thus demonstrates that IL-22BP promotes bacterial uptake into PPs by influencing FAE gene expression and function.

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Citations

Oct 28, 2017·Journal of Gastroenterology·Atsushi MizoguchiEmiko Mizoguchi
Jul 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam K SavageRichard M Locksley
Jan 18, 2018·The Journal of Experimental Medicine·Takashi KanayaHiroshi Ohno
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Sep 2, 2021·Mucosal Immunology·Cécilia LucianiHugues Lelouard

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Methods Mentioned

BETA
IECs
IEC
nuclear translocation
ELISA
flow cytometry
PCR
in vitro transcription
Assay

Software Mentioned

MetaMorph
UCHIME
FlowJo
Miseq
Tree Star
QIIME
RDPclassifier

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