Dagur PK, Biancotto A, Wei L, et al.MCAM-expressing CD4(+) T cells in peripheral blood secrete IL-17 A and are significantly elevated in inflammatory autoimmune diseases. J Autoimmun 37:319-327

Hematology Branch, National Heart Lung and Blood Institute, Bethesda, MA 20892, USA.
Journal of Autoimmunity (Impact Factor: 8.41). 09/2011; 37(4):319-27. DOI: 10.1016/j.jaut.2011.09.003
Source: PubMed


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.

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    • "CD146 is a marker for circulating endothelial cells. The increased levels of CD146 are positively correlated with active inflammatory reactions in idiopathic myopathy [55], chronically inflamed tissues [56], inflammatory skin disease [57], rheumatoid arthritis [58], inflammatory bowel disease [59,60], chronic obstructive pulmonary disease [61], and multiple sclerosis disease [62,63]. The engagement of CD146 initiates the protein kinase phosphorylation cascade through association with Fyn, a Src family kinase. "
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    • "Herein we report the identification of Melanoma cell adhesion molecule (MCAM) as an adhesion receptor on TH17 cells in the circulation, and we identify a major tissue ligand for MCAM as laminin 411, which is expressed selectively by vascular endothelial cells. Our results with MCAM expression on TH17 cells independently confirms and extends a recent report by Dagur, et al., and is consistent with previous reports that MCAM supports cell interactions within the vasculature [9], [10], [11], [12]. Our novel results with laminin 411 offers insight into how MCAM on TH17 cells may function within the adhesion cascade. "
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