气候变化领域集成服务门户(CCPortal): ICOS ligand and IL-10 synergize to promote host

CCPortal

DOI	10.1073/pnas.2018278118
	ICOS ligand and IL-10 synergize to promote host–microbiota mutualism
	Landuyt A.E.; Klocke B.J.; Duck L.W.; Kemp K.M.; Muir R.Q.; Jennings M.S.; Blum S.I.; Tse H.M.; Lee G.; Morrow C.D.; Elson C.O.; Maynard C.L.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Genome-wide association studies have identified ICOSLG, which encodes the inducible costimulator ligand (ICOSLG or ICOSL) as a susceptibility locus for inflammatory bowel disease. ICOSL has been implicated in the enhancement of pattern recognition receptor signaling in dendritic cells, induction of IL-10 production by CD4 T cells, and the generation of high-affinity antibodies to specific antigens—all of which can potentially explain its involvement in gastrointestinal inflammation. Here, we show that murine ICOSL deficiency results in significant enrichment of IL-10–producing CD4 T cells particularly in the proximal large intestine. Transient depletion of IL-10–producing cells from adult ICOSL-deficient mice induced severe colonic inflammation that was prevented when mice were first treated with metronidazole. ICOSL-deficient mice displayed reduced IgA and IgG antibodies in the colon mucus and impaired serum antibody recognition of microbial antigens, including flagellins derived from mucus-associated bacteria of the Lachnospiraceae family. Confirming the synergy between ICOSL and IL-10, ICOSL deficiency coupled with CD4-specific deletion of the Il10 gene resulted in juvenile onset colitis that was impeded when pups were fostered by ICOSL-sufficient dams. In this setting, we found that both maternally acquired and host-derived antibodies contribute to the life anti-commensal antibody repertoire that mediates this protection in early life. Collectively, our findings reveal a partnership between ICOSL-dependent anti-commensal antibodies and IL-10 in adaptive immune regulation of the microbiota in the large intestine. Furthermore, we identify ICOSL deficiency as an effective platform for exploring the functions of anti-commensal antibodies in host–microbiota mutualism. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Anti-commensal antibodies; ICOSL; IL-10; Microbiota
语种	英语
scopus关键词	CD4 antigen; cytokine; flagellin; immunoglobulin A antibody; immunoglobulin G antibody; inducible T cell costimulator ligand; interleukin 10; metronidazole; adaptive immunity; adult; animal cell; animal experiment; animal model; animal tissue; antibody blood level; Article; CD4+ T lymphocyte; colitis; controlled study; cytokine production; female; host microbe interaction; Lachnospiraceae; large intestine; male; mouse; nonhuman; priority journal; protein depletion; symbiosis
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180065
作者单位	Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States
推荐引用方式 GB/T 7714	Landuyt A.E.,Klocke B.J.,Duck L.W.,等. ICOS ligand and IL-10 synergize to promote host–microbiota mutualism[J],2021,118(13).
APA	Landuyt A.E..,Klocke B.J..,Duck L.W..,Kemp K.M..,Muir R.Q..,...&Maynard C.L..(2021).ICOS ligand and IL-10 synergize to promote host–microbiota mutualism.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Landuyt A.E.,et al."ICOS ligand and IL-10 synergize to promote host–microbiota mutualism".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).