The underlying mechanisms are not yet fully understood, but IL-10 may directly dampen MyD88-dependent proinflammatory signaling by ubiquitination and degradation of IRAK4 and TRAF6.158 Conversely, absence of MyD88 protects IL-10-deficient mice against the development of spontaneous enterocolitis by inhibiting downstream NF-κB-dependent TH1/TH17 polarization.159,160 Similarly, commensal-dependent expansion of colitogenic CD4+ TH17 cells is also impaired in Rag-2−/− mice transferred with MyD88−/− CD4+CD45RBhi cells, resulting in significant delay in onset of spontaneous colitis.27,28. Here, MYD88 is linked to enterocolitis.