TY - JOUR
T1 - A commensal symbiotic factor derived from Bacteroides fragilis promotes human CD39+Foxp3+ T cells and Treg function
AU - Telesford, Kiel M.
AU - Yan, Wang
AU - Ochoa-Reparaz, Javier
AU - Pant, Anudeep
AU - Kircher, Christopher
AU - Christy, Marc A.
AU - Begum-Haque, Sakhina
AU - Kasper, Dennis L.
AU - Kasper, Lloyd H.
N1 - Publisher Copyright:
© 2015, Taylor & Francis Group, LLC.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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 (Tregs). However, PSA-mediated induction of Foxp3 in humans has not been reported. In mice, PSA-generated Foxp3+ Tregs 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 naïve 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+ Tregs, PSA enriched Foxp3 expression, enhanced the frequency of CD39+HLA-DR+ cells, and increased suppressive function as measured by decreased TNFα 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+ Tregs 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.
AB - 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 (Tregs). However, PSA-mediated induction of Foxp3 in humans has not been reported. In mice, PSA-generated Foxp3+ Tregs 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 naïve 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+ Tregs, PSA enriched Foxp3 expression, enhanced the frequency of CD39+HLA-DR+ cells, and increased suppressive function as measured by decreased TNFα 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+ Tregs 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.
KW - Autoimmunity
KW - Bacteroides fragilis
KW - Commensal microbiota
KW - Dendritic cell
KW - Ectonuclease
KW - Foxp3
KW - Multiple sclerosis
KW - T regulatory cells
KW - Zwitterionic polysaccharide
UR - http://www.scopus.com/inward/record.url?scp=84944445669&partnerID=8YFLogxK
UR - https://doi.org/10.1080/19490976.2015.1056973
U2 - 10.1080/19490976.2015.1056973
DO - 10.1080/19490976.2015.1056973
M3 - Article
C2 - 26230152
AN - SCOPUS:84944445669
SN - 1949-0976
VL - 6
SP - 234
EP - 242
JO - Gut Microbes
JF - Gut Microbes
IS - 4
ER -