Increased numbers of immature plasma cells in peripheral blood specifically overexpress chemokine receptor CXCR3 and CXCR4 in patients with ulcerative colitis

Abstract

SummaryUlcerative colitis (UC) is a chronic inflammatory bowel disease featuring infiltration by plasma cells producing immunoglobulins. We have reported previously the specific and significant proliferation of immature plasma cells in the inflamed colonic and pouch mucosa of UC patients. The aim of this study was to characterize peripheral blood immature plasma cells and the migration mechanisms of such immature plasma cells to inflamed sites in UC. The characteristics of peripheral blood immature plasma cells and chemokine receptor expression were examined by flow cytometry. Expression of mucosal chemokine was quantified using real-time reverse transcription-polymerase chain reaction and immunohistochemistry. The number of peripheral blood immature plasma cells was significantly higher in patients with active UC and active Crohn's disease (CD) than in healthy controls. The proportion of immature plasma cells was correlated positively with clinical activities of UC and CD. Many peripheral blood immature plasma cells were positive for CXCR3, CXCR4, CCR9 and CCR10. Expression of CXCR3 and CXCR4 in UC patients was significantly higher than in controls. CXCL9, CXCL10 and CXCL11 mRNA levels in colonic mucosa of inflamed IBD were higher than in controls. Immunofluorescence study also showed abundant CXCR3-positive immature plasma cells in the inflamed colonic mucosa of UC. Increased numbers of immature plasma cells may migrate towards inflammatory sites of UC via the CXCR3 axis, and may participate in UC pathogenesis.

CD8 T cells induce T-bet–dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines

“…32, 44 Yet it is not clear whether CXCR3 expressed by autoreactive B cells confers them with migratory properties that enable them to cause harm, either through antibody production or promoting inflammation through cytokine release. The existence of high frequencies of CXCR3 ϩ AFCs or memory B cells in the blood of patients with autoimmune disorders 16,17 supports the hypothesis that migration and survival of postmitotic self-reactive AFCs, or plasma cells, are favored at sites of chronic inflammation through a mechanism implicating CXCR3 ligands. 18,45 Thus, autoantibodies may be produced by fully differentiated long-lived CXCR3 ϩ plasma cells recruited and persisting in inflamed tissues.…”

“…14,15 CXCR3 ϩ AFCs and memory B cells were found at particularly high frequency in peripheral blood of patients with autoimmune diseases mediated by autoantibodies. 16,17 This suggests that selfreactive AFCs may be produced and/or attracted to and sustained in chronic inflammatory niches through a mechanism that involves CXCR3 and its ligands. 18 In mouse models for lupus erythematosus, AFCs are found in inflamed tissues.…”

Organ-specific migration of mesenchymal stromal cells: Who, when, where and why?

“…It was shown that levels of CXCR4 and CXCL12 are up-regulated in patients with inflammatory bowel disease [92]. Lentiviral over-expression of CXCR4 in MSC resulted in enhanced homing to the inflamed colon and amelioration of disease severity in TNBS-treated rats [93].…”

Utility of Flow Cytometry to Classify Abnormal Plasma Cell Populations in Marrow Samples Collected from Patients with Putative Plasma Cell Neoplasms

“…In one study, patients with SLE were found to have decreased non-switched memory B cells; however these cells had increased CXCR4 expression and elevated serum SLE auto-antibodies, suggesting that the B cells had a more plasma cell like phenotype [25]. In a study of patients with inflammatory bowel disease, patients with ulcerative colitis or Crohn's disease were more likely to have circulating peripheral blood immature plasma cells with higher CXCR4 expression [26].…”