MCAM-expressing CD4+ T cells in peripheral blood secrete IL-17A and are significantly elevated in inflammatory autoimmune diseases

Th17 cells are a subset of CD4+ T cells characterized by production of IL-17 and are known to be key participants in inflammatory reactions and various autoimmune diseases. In this study we found that a subset of human CD4+ T cells expressing MCAM (CD146) have higher mRNA levels of RORC2, IL-23R, IL-26, IL-22, IL-17A, but not IFN-γ, compared to CD4+ T cell not expressing CD146. Upon TCR stimulation with CD3/CD28, CD4+CD146+ T cells secrete significantly more IL-17A, IL-6, and IL-8 than do CD4+CD146− T cells. Low frequencies of CD4+CD146+ T cells are found in the circulation of healthy adults, but the frequency of these cells is significantly increased in the circulation of patients with inflammatory autoimmune diseases including Behcet’s, sarcoidosis and Crohn’s disease. Patterns of gene expression and cytokine secretion in these cells are similar in healthy and disease groups. In Crohn’s disease, the increase in CD4+CD146+ cells in the circulation correlates with disease severity scores. These data indicate that expression of CD146 on CD4+ T cells identifies a population of committed human Th17 cells. It is likely the expression of CD146, an endothelial adhesion molecule, facilitates adherence and migration of Th17 cells through the endothelium to sites of inflammation.

► CD146+ CD4+ T cells secrete IL-17A and display multiple features of Th17 cells. ► CD146+ CD4+ T cells do not require polarization to become TH17 cells. ► These cells are in low levels in the blood of healthy donors. ► CD146+ CD4+ T cells levels significantly increase in inflammatory autoimmune diseases. ► Lymphocytes expressing CD146 have been shown to have enhanced binding to endothelium.