Animal study demonstrates that excessive endosomal TLR signaling drives severe colitis in LRBA-deficient mice, indicating innate immune pathways aggravate gut inflammation.
Significance IBD is one of the most common early manifestations of LRBA deficiency and has been attributed to impaired regulatory T cell function. However, whether other immune cell types also contribute has not been comprehensively tested. We found that, in LRBA-deficient mice, DCs contribute significantly to colitis in the DSS model. We also showed that blocking innate immune signaling from the endosomal TLRs, TLR3, TLR7, and TLR9, in Lrba −/− mice dramatically reduced their susceptibility to DSS-induced colitis. Our data indicate a role for LRBA in limiting endosomal TLR signaling and suggest that elevated IRF3 and IRF7 activation leading to increased expression of inflammatory chemokines promotes excessive intestinal inflammation in LRBA-deficient mice.
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Wang et al. (2019) studied this question.
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