CD6 Receptor Regulates Intestinal Ischemia/Reperfusion-induced Injury by Modulating Natural IgM-producing B1a Cell Self-renewal

Abstract

Edited by Luke O'NeillIntestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease is poorly understood, although it is established that circulating pathogenic natural IgM, which is primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as a marker for T cells and was later found to be present on some subsets of B cells in humans; however, whether CD6 plays any role in intestinal I/R-induced injury and, if so, the underlying mechanisms, remain unknown. Here we report that CD6؊/؊ mice were significantly protected from intestinal inflammation and mucosal damage compared with WT mice in a model of intestinal I/R-induced injury. Mechanistically, we found that CD6 was selectively expressed on B1 cells outside of the bone marrow and peritoneal cavity and that pathogenic natural IgM titers were reduced in the CD6 ؊/؊ mice in association with significantly decreased B1a cell population. Our results reveal an unexpected role of CD6 in the pathogenesis of intestinal IR-induced injury by regulating the self-renewal of B1a cells.

CD6 as a potential target for treating multiple sclerosis

“…Our latest studies of B cells in CD6 KO mice showed that, unlike in humans, CD6 is not expressed on any of the B2 cells (specifically marginal and follicular B cells) in mice, neither constitutively nor after activation (33). Instead, mouse CD6 is selectively expressed on a small subset of B1a cells found in the spleen, liver, and peripheral blood, but not in the bone marrow or peritoneal cavity.…”

Identification of the First Teleost CD5 Molecule: Additional Evidence on Phenotypical and Functional Similarities between Fish IgM+ B Cells and Mammalian B1 Cells

“…To provide additional evidence that might help us establish to what extent this hypothesis can be confirmed, we identified in rainbow trout (Oncorhynchus mykiss) a homolog of CD5 and demonstrated that a major fraction of trout splenic B cells express CD5 on the cell surface. Additionally, we identified a homolog of CD6, another member of the SRCR family of receptors recently described to be selectively expressed on mammalian splenic B1a cells (30) and T cells (31), demonstrating that fish B cells also transcribe CD6. Further phenotypical and functional characterization of fish B cells in parallel to murine splenic B2 cells clearly established a resemblance of fish IgM + B cell responses to mammalian B1 cell responses regardless of CD5 surface expression.…”

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

“…Intestinal ischaemia/reperfusion (II/R) injury is closely related to mesenteric ischaemia, haemorrhagic shock, and organ transplantation (Enyindah‐Asonye et al, ; X. H. Liu et al, ; Matsuo, Chaung, Liou, Wang, & Yang, ; W. Zhou et al, ). Intestinal ischaemia can cause cell damage and provoke epithelial barrier dysfunction during reperfusion, resulting in systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and death (Duranti et al, ; Feng et al, ; Impellizzeri et al, ).…”

“…Intestinal ischaemia/reperfusion (II/R) injury is closely related to mesenteric ischaemia, haemorrhagic shock, and organ transplantation (Enyindah-Asonye et al, 2017;X. H. Liu et al, 2015;Matsuo, Chaung, Liou, Wang, & Yang, 2018;W.…”