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
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 i...
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doaj-8f915895408249d8be9debdce48a6b632020-11-24T21:20:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-06-01910.3389/fimmu.2018.01503379317Elevated 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 ColitisGufang Zhang0Jin Liu1Lehao Wu2Lehao Wu3Yu Fan4Lei Sun5Feng Qian6Daijie Chen7Richard D. Ye8Richard D. Ye9School of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaInstitute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, ChinaInstitute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaInstitute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, ChinaInduced 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 improves colonic epithelial integrity. These findings suggest that in the DSS-induced mouse colitis model, SAA isoforms are expressed to different extent in colon and deletion of Saa3 renders these mice more susceptible to DSS-induced injury. The presence of SAA3 in the inflamed colon mucosal serves to protect epithelial barrier in part through expansion of IL-22-producing neutrophils. It is speculated that SAA3 stimulation of autologous neutrophils may have therapeutic potential for inflammatory bowel disease.https://www.frontiersin.org/article/10.3389/fimmu.2018.01503/fullserum amyloid Ainflammationinnate immunitycytokinescolitisneutrophils |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gufang Zhang Jin Liu Lehao Wu Lehao Wu Yu Fan Lei Sun Feng Qian Daijie Chen Richard D. Ye Richard D. Ye |
spellingShingle |
Gufang Zhang Jin Liu Lehao Wu Lehao Wu Yu Fan Lei Sun Feng Qian Daijie Chen Richard D. Ye Richard D. Ye 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 serum amyloid A inflammation innate immunity cytokines colitis neutrophils |
author_facet |
Gufang Zhang Jin Liu Lehao Wu Lehao Wu Yu Fan Lei Sun Feng Qian Daijie Chen Richard D. Ye Richard D. Ye |
author_sort |
Gufang Zhang |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-06-01 |
description |
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 improves colonic epithelial integrity. These findings suggest that in the DSS-induced mouse colitis model, SAA isoforms are expressed to different extent in colon and deletion of Saa3 renders these mice more susceptible to DSS-induced injury. The presence of SAA3 in the inflamed colon mucosal serves to protect epithelial barrier in part through expansion of IL-22-producing neutrophils. It is speculated that SAA3 stimulation of autologous neutrophils may have therapeutic potential for inflammatory bowel disease. |
topic |
serum amyloid A inflammation innate immunity cytokines colitis neutrophils |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01503/full |
work_keys_str_mv |
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