The Contribution of CD40/CD40L Axis in Inflammatory Bowel Disease: An Update

Abstract

Inflammatory bowel disease (IBD) is a chronic and multifactorial disease of the gastrointestinal tract. The exact etiology of IBD remains complex and unclear involving an inadequately defined relationship between microbial insult, genetic predisposition, altered intestinal barrier permeability, oxidative stress components and abnormal immune responses. The role of the co-stimulatory system made up of cluster of differentiation 40 protein (CD40) and its ligand (CD40L) in the response of the immune system to pathogens is now widely accepted. The implication of CD40/CD40L axis in immune system disorders due to its important role as signal transduction pathway among immune cells is well documented. Several studies have suggested that CD40/CD40L interactions regulate oxidative stress; this can affect various signaling pathways leading to IBD development. Hence, CD40/CD40L signaling pathway may become a new target for IBD treatment. This review will cover the general contribution of the CD40/CD40L dyad in the development of IBD in order to facilitate future approaches aiming to elucidate the immunological mechanisms that control gut inflammation.

Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease

“…As such, macrophage-associated genes downregulated in response to vedolizumab included the costimulatory molecule CD40,50 chemokines ( CXCL9 , CXCL11 , CXCL13 ), phospholipase A1 member A ( PLA1A1 ), which is increased in expression in CD and contributes to the production of proinflammatory lysophospholipids,51 signalling lymphocytic activation molecule (SLAM/ SLAMF1 ), which contributes to myeloid-derived inflammatory cytokine production,52 and proinflammatory chitinase 3-like-1 ( CHI3L1 ,53) (figure 7G). In contrast, we observed increased expression of ADAMDEC1 , a disintegrin and metalloproteinase (ADAM) family member that inhibits intestinal inflammation54 (figure 7G).…”

The Role of Dendritic Cell Maturation in the Induction of Insulin-Dependent Diabetes Mellitus

“…The CD154 ligand for CD40R is briefly synthesized on the membrane of activated CD4 + T cells and is also synthesized on immune cells involved in the development of autoimmunity (64, 65). Interactions between CD40R and its ligand CD154 results in movement of CD40R into cholesterol-rich membrane microdomains and the binding of TNFR-associated factors (TRAFs) to its cytoplasmic tail as recently described by Senhaji et al (66) and others (61, 67–71). The CD40R receptor was also shown to directly bind TRAF2, TRAF3, TRAF5, and TRAF6 and to indirectly associate with TRAF1 (61, 68, 72) (Figure 1).…”

Nanovesicle-targeted Kv1.3 knockdown in memory T cells suppresses CD40L expression and memory phenotype

“…This crosstalk between hyperactive T cells, B cells and DCs, which is accentuated by CD40L overexpression, constitutes a vicious circle in SLE patients, and ultimately leads to disease flare and end-stage organ damage. Enhanced T cell receptor (TCR)-mediated Ca 2+ influx and CD40L expression have also been reported in IBD and contribute to the development of the disease [5, 15]. …”