Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD’s clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.

Study on the Characteristics of Coarse Feeding Tolerance of Ding’an Pigs: Phenotypic and Candidate Genes Identification

“…CD6 is predominantly expressed by peripheral T lymphocytes, myeloid thymocytes, and B1a lymphocytes, constituting a type I transmembrane glycoprotein. It exerted an inhibitory effect on T-cell activation while also promoting colonic inflammatory responses [51,52]. Knockout of TAP1 in mice led to the activation of their natural cell-killing capacity [53,54].…”

Genome-Wide Comparative Analysis of SRCR Gene Superfamily in Invertebrates Reveals Massive and Independent Gene Expansions in the Sponge and Sea Urchin

“…SRCR domains are divided into Group A and Group B based on the number and position of conserved cysteine residues [16,17], with Group A having six cysteine residues that form three pairs of disulfide bonds, and Group B having eight cysteine residues that form four pairs of disulfide bonds [18]. For instance, CD5 (cluster of differentiation 5) [19], CD6 (cluster of differentiation 6) [20], and DMBT1 (deleted in malignant brain tumor 1) [21] belong to Group B, whereas MARCO (macrophage receptor with collagenous structure) [22], Mac2BP (Mac-2 binding protein) [23], and LOX (lysyl oxidase) family (LOX-like 2, LOX-like 3, and LOX-like 4) [24] belong to Group A. Until now, research on SRCR-SFs within Group B has primarily focused on vertebrates, with only one reported instance in the invertebrate Geodia cydonium [25].…”