Neuropilin-1 surface expression discriminates between nT reg cells with stable expression and Nrp1 low iT reg cells showing inducible expression under inflammatory conditions.

T-helper-17 (Th17) cells have critical roles in mucosal defense and in autoimmune disease pathogenesis 1-3. They are most abundant in the small intestine lamina propria (SILP), where their presence requires colonization of mice with microbiota 4-7. Segmented Filamentous Bacteria (SFB) are sufficient to induce Th17 cells and to promote Th17-dependent autoimmune disease in animal models 8-14. However, the specificity of Th17 cells, the mechanism of their induction by distinct bacteria, and the means by which they foster tissue-specific inflammation remain unknown. Here we show that the T cell receptor (TCR) repertoire of intestinal Th17 cells in SFB-colonized mice has minimal overlap with that of other intestinal CD4+ T cells and that most Th17 cells, but not other T cells, recognize antigens encoded by SFB. T cells with antigen receptors specific for SFB-encoded peptides differentiated into RORγt-expressing Th17 cells, even if SFB-colonized mice also harbored a strong Th1 cell inducer, Listeria monocytogenes, in their intestine. The match of T cell effector function with antigen specificity is thus determined by the type of bacteria that produce the antigen. These findings have significant implications for understanding how commensal microbiota contribute to organ-specific autoimmunity and for developing novel mucosal vaccines.

Generation of anaphylaxis-inducing high affinity IgE requires sequential class switching.

Summary Infection with the opportunistic enteric pathogen Clostridium difficile is an increasingly common clinical complication that follows antibiotic treatment-induced gut microbiota perturbation. Innate lymphoid cells (ILCs) are early responders to enteric pathogens; however, their role during C. difficile infection is undefined. To identify immune pathways that mediate recovery from C. difficile infection, we challenged C57BL/6, Rag1−/−, which lack T and B cells, and Rag2−/− Il2rg−/− (Ragγc−/−) mice, which additionally lack ILCs, with C. difficile. In contrast to Rag1−/− mice, ILC-deficient Ragγc−/− mice rapidly succumbed to infection. Rag1−/−, but not Ragγc−/− mice, upregulate expression of ILC1 or ILC3 associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Ragγc−/− mice. While ILC3s made a minor contribution to resistance, loss of IFN-γ or T-bet-expressing ILC1s in Rag1−/− mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile.