Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3+ regulatory T cells

Verma, Ravi; Lee, Changhon; Jeun, Eun-Ji; Yi, Jaeu; Kim, Kwang Soon; Ghosh, Ambarnil; Byun, Seohyun; Lee, Choong-Gu; Kang, Hye-Ji; Kim, Gi-Cheon; Jun, Chang-Duk; Jan¨, Gwénaël,; Suh, Chang-Hee; Jung, Ju-Yang; Sprent, Jonathan; Rudra, Dipayan; De Castro, Cristina; Molinaro, Antonio; Surh, Charles D.; Im, Sin-Hyeog

Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3+ regulatory T cells

2018

Dysregulation of intestinal microflora is linked to inflammatory disorders associated with compromised immunosuppressive functions of Foxp3+ T regulatory (Treg) cells. Although mucosa-associated commensal microbiota has been implicated in Treg generation, molecular identities of the “effector” components controlling this process remain largely unknown. Here, we have defined Bifidobacterium bifidum as a potent inducer of Foxp3+ Treg cells with diverse T cell receptor specificity to dietary antigens, commensal bacteria, and B. bifidum itself. Cell surface β-glucan/galactan (CSGG) polysaccharides of B. bifidum were identified as key components responsible for Treg induction. CSGG efficiently recapitulated the activity of whole bacteria and acted via regulatory dendritic cells through a partially Toll-like receptor 2–mediated mechanism. Treg cells induced by B. bifidum or purified CSGG display stable and robust suppressive capacity toward experimental colitis. By identifying CSGG as a functional component of Treg-inducing bacteria, our studies highlight the immunomodulatory potential of CSGG and CSGG-producing microbes.

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