IndraLab

"As TNFAIP3 normally restricts inflammatory TLR signals and its expression is induced in a variety of tissue types XREF_BIBR, XREF_BIBR, XREF_BIBR, the increased gut permeability in TNFAIP3 -/- mice might reflect an indirect effect of ongoing inflammation in these mice, a direct role for TNFAIP3 in IEC TJ stability, or a combination of these two effects."

"As mentioned earlier, Tnfaip3 −/− mice develop spontaneous multi-organ inflammation that leads to premature lethality. xref Tnfaip3 −/− mice on a Rag1 −/− background still developed spontaneous inflammation, indicating that adaptive lymphocytes were not essential for the uncontrolled inflammatory response, xref although hematopoietic cells were clearly involved. xref Signals from TNF were similarly dispensable for the inflammation in Tnfaip3 −/− mice, and A20 potently inhibited TLR signaling in macrophages. xref Consistent with these observations, homeostatic TLR signaling dependent on the Myd88 adaptor was dysregulated in A20-deficient mice. xref The homeostatic Myd88-dependent signals were derived from commensal intestinal bacteria since treatment of Tnfaip3 −/− mice with broad spectrum antibiotics reduced systemic inflammation and prevented cachexia. xref A20 is therefore a critical regulator of immune homeostasis and TLR signaling in vivo ."

"On the other hand, TNFAIP3 can inhibit TLR induced activity of NFkappaB by de-ubiquitination of TRAF6."

"TNFAIP3 ( A20 ) and NFKBIA regulate NF-kB activation , downregulating TLR signals , and cytokine production.29-31 Analysis of RNA-seq data of HMCs before and after dFB co-culture for the same 22 genes with DE in the FANTOM5 set revealed that most of the modulated genes were similarly altered in our mRNA-seq analysis ( Figure 6B ) ."