期刊
GUT MICROBES
卷 6, 期 4, 页码 234-242出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/19490976.2015.1056973
关键词
autoimmunity; Bacteroides fragilis; commensal microbiota; dendritic cell; ectonuclease; Foxp3; multiple sclerosis; T regulatory cells; zwitterionic polysaccharide
资金
- National Multiple Sclerosis Society [RG 4662A2/1]
- National Institutes of Health [1R 41AI110170-01]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R41AI110170] Funding Source: NIH RePORTER
Polysaccharide A (PSA) derived from the human commensal Bacteroides fragilis is a symbiosis factor that stimulates immunologic development within mammalian hosts. PSA rebalances skewed systemic T helper responses and promotes T regulatory cells (T-reg). However, PSA-mediated induction of Foxp3 in humans has not been reported. In mice, PSA-generated Foxp3(+) T-reg dampen Th17 activity thereby facilitating bacterial intestinal colonization while the increased presence and function of these regulatory cells may guard against pathological organ-specific inflammation in hosts. We herein demonstrate that PSA induces expression of Foxp3 along with CD39 among naive CD4 T cells in vitro while promoting IL-10 secretion. PSA-activated dendritic cells are essential for the mediation of this regulatory response. When cultured with isolated Foxp3(+) T-reg, PSA enriched Foxp3 expression, enhanced the frequency of CD39(+)HLA-DR+ cells, and increased suppressive function as measured by decreased TNF alpha expression by LPS-stimulated monocytes. Our findings are the first to demonstrate in vitro induction of human CD4(+) Foxp3(+) T cells and enhanced suppressive function of circulating Foxp3(+)T(reg) by a human commensal bacterial symbiotic factor. Use of PSA for the treatment of human autoimmune diseases, in particular multiple sclerosis and inflammatory bowel disease, may represent a new paradigm in the approach to treating autoimmune disease.
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