Elevated Expression of Serum Amyloid A 3 Protects Colon Epithelium Against Acute Injury Through TLR2-Dependent Induction of Neutrophil IL-22 Expression in a Mouse Model of Colitis

Frontiers in Immunology
Gufang ZhangRichard D Ye

Abstract

Induced expression of serum amyloid A (SAA) is a hallmark of many inflammatory diseases, but whether SAA exacerbates inflammation or protects tissues against injury remains unclear. In dextran sulfate sodium (DSS)-induced colitis, SAA3 is the predominant isoform of inducible SAA proteins that also include SAA1 and SAA2, and mice with genetic deletion of Saa3 exhibits increased production of proinflammatory cytokines, decreased expression of IL-22 along with aggravated epithelium disruption, and reduced colon length compared with wild-type littermates. Colonic neutrophils have been identified as a major source of IL-22 in these mice. Administration of exogenous SAA3 as recombinant protein to Saa3-/- mice improves neutrophil IL-22 production, colonic epithelial integrity, and secretion of the antimicrobial peptides Reg3β and Reg3γ. Stimulation of mouse bone marrow neutrophils with mouse SAA3 or human SAA1 leads to expansion of IL-22-producing neutrophils. Unlike previously reported IL-22 induction through IL-23, the SAA3-induced neutrophil IL-22 expression utilizes a TLR2-dependent mechanism that does not depend on IL-23. Adoptive transfer of the SAA3-treated neutrophils to Saa3-/- mice ameliorates DSS-induced colitis and improve...Continue Reading

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Citations

Sep 12, 2019·Immunology·Amelia T Soderholm, Virginia A Pedicord
Dec 19, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yu FanRichard D Ye
May 5, 2020·IUBMB Life·Mojtaba ShohanNader Bagheri
Aug 2, 2019·World Journal of Gastroenterology : WJG·Sandra Vidal-LletjósAnnaïg Lan
Nov 22, 2019·Frontiers in Molecular Biosciences·Kuldeep DhamaSunil Kumar Joshi
Dec 15, 2020·Immunology·Sara Abouelasrar SalamaSofie Struyf
Jun 3, 2021·Animals : an Open Access Journal From MDPI·Sato KamiyaYasuo Inoshima

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Methods Mentioned

BETA
DNA array
Knockout
flow cytometry
density gradient equilibrium centrifugation
protein Assay
Infrared Imaging
ELISA
PCR

Software Mentioned

NIH Image J
Prism
GraphPad

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