Over 5 Mio. IBD patients endure lifelong relapses despite treatment. 4% of severe monogenic IBD cases are linked to XIAP deficiency. I characterized inflammation and dysbiosis in Xiap-/- mice. CD209a+ DC subsets in the ileum drive inflammation via aberrant TNF signalling through TNFR2. Xiap-/- mice show signs of dysbiosis and metabolic profile changes. This reveals XIAP's crucial role in mediating local innate immune responses. This may help refine IBD treatment by targeting mechanisms of inflammatory cell death, and microbiota-based therapies.
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