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Consistently, we found that LPS induced more cell death and significantly higher levels of IL-1α and IL-1β in HoipDC KO cells. Importantly, MyD88 deficiency rescued the inflammatory phenotype in HoipDC KO mice. Together, these findings reveal the indispensable function of HOIP in maintaining DC homeostasis, and MyD88-dependent proinflammatory signal plays a substantial role in the pathogenesis of human autoinflammation associated with HOIP mutations.SIGIRR has been described as a negative regulator of several IL-1R/TLR family members a