Details

Autor(en) / Beteiligte

• Geem, Duke
• Medina‐Contreras, Oscar
• Newberry, Rodney
• Denning, Timothy Luke

Titel

Microbiota‐Dependent Th17 and Foxp3+ Regulatory T Cell Differentiation in the Intestinal Lamina Propria

Ist Teil von

• The FASEB journal, 2013-04, Vol.27 (S1)

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Abstract only The intestinal microbiota regulates the development and function of mucosal and systemic immune responses. Segmented filamentous bacteria (SFB) and Clostridium strains have been implicated in the development of intestinal Th17 cells and Foxp3+ regulatory T (Treg) cells, respectively, yet the mechanisms and location of their differentiation remains incompletely understood. Using lymphotoxin‐alpha knockout mice, which are deficient in secondary lymphoid organs (SLO)‐including gut‐associated lymphoid structures, we examined the influence of the microbiota on CD4+ T cell differentiation directly in the intestinal lamina propria. Our data demonstrate that CD4 single‐positive thymocytes adoptively transferred into congenic recipients were capable of rapidly migrating to the intestinal lamina propria. Consistent with these observations, naïve CD4+ T cells were abundant in the intestines of both adult gnotobiotic mice and early postnatal SPF mice, and bacterial colonization of either group induced differentiation of Foxp3+ Treg cells, as detected by flow cytometry. Oral gavage of SFB‐containing microbiota into SFB‐free mice was also sufficient to drive Th17 differentiation in mice void of SLO. Collectively, these data suggest that specific components of the microbiota are capable of inducing the development of effector and regulatory T cell subsets directly in the intestinal lamina propria. Supported by an Emory Children's Pediatric Center Seed Grant to T.L.D. a Research Fellowship Award from the Crohn's and Colitis Foundation of America to O.M.C. and a F30 NIH NRSA Fellowship to D.G.