Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon.
Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Seong Gyu
SG
Jeon
Hisako
H
Kayama
Yoshiyasu
Y
Ueda
Takuya
T
Takahashi
Takashi
T
Asahara
Hirokazu
H
Tsuji
Noriko M
NM
Tsuji
Hiroshi
H
Kiyono
Ji Su
JS
Ma
Takashi
T
Kusu
Ryu
R
Okumura
Hiromitsu
H
Hara
Hiroki
H
Yoshida
Masahiro
M
Yamamoto
Koji
K
Nomoto
Kiyoshi
K
Takeda
D019264:Adoptive Transfer; D000818:Animals; D039941:Bifidobacteriales Infections / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D001644:Bifidobacterium / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D002454:Cell Differentiation; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D003106:Colon / Q000276:immunology / Q000382:microbiology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions; D016867:Immunocompromised Host; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007780:Lacticaseibacillus casei / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019936:Probiotics / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
C508609:IL10 protein, human; D016753:Interleukin-10