We addressed the functional role of microbiota in experimental contact hypersensitivity (CHS), a CD8+ Tc1–mediated cutaneous inflammatory model, which largely resembles allergic contact dermatitis in men. We found that germfree mice (GF) exhibited reduced ear swelling and cellular infiltration compared to conventionally housed (Conv) mice. To our surprise, hapten–specific Tc1 responses (proliferation, IFNγ production) were not altered in Conv and GF animals, excluding an effect of microbial stimualtion on T cell priming. Importantly, recolonized GF mice showed an unaffected CHS reaction, excluding a general defect in the GF immune system and a potent CHS–stimulatory capacity for microbiota in general. However, lymphocytes from skin–draining lymph nodes of CHS tolerant GF mice secreted higher amounts of IL10. Unexpectedly, ablation of the intestinal microbiota in mice, by an antibiotics (ABX) cocktail, completely mimicked the GF phenotype with regard to clinical symptoms, T cell response and IL10 secretion. This indicates that intestinal– but not cutaneous– microbiota shape immunity towards contact allergens. Moreover, a distinct set of bacteria was able to restore CHS immunity in total. Indicating that extent and quality of bacterial stimulation in the gut alter hapten–driven skin inflammation. Increased numbers of IL10 producing CD25+ CD4+ T cells and restoration of CHS responses in the absence of IL10 producing FOXP3+ Tregs in ABX treated mice demonstrated the functional relevance of T cell related IL10 in CHS inhibition. In absence of TLR2 signaling, the CHS response was restored in germ reduced mice. Interestingly, GF and ABX conditions restored IL10 secretion in TLR2 –deficient mice, demonstrating a role for TLR2 engagement upstream of Treg IL10 production.

ESDR188 - Bacterial stimulation in the gut shapes hapten–driven skin inflammation

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING