Ubiquitination of the IKK complex mediated via proteins IRAK and TRAF-6 is an important step in the activation of the NF-kB pathway that plays a critical role in the immune response to microbes including the transcription of pro-inflammatory genes such as IL-2, IL-6, IL-12, TNFα, activation of macrophages and differentiation of CD4+ T cells.101 Increased activation of this pathway has been demonstrated as an important driver of IBD.102 Furthermore, the gut microbiota has been shown to modulate the expression of this signaling cascade and thus directly influence gut inflammation.103–105. Here, CD4 is linked to inflammatory bowel disease.