title: MCAM-expressing CD4(+) T cells in peripheral blood secrete IL-17A and are significantly elevated in inflammatory autoimmune diseases.
abstract: 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.
authors.affiliation: Hematology Branch, National Heart Lung and Blood Institute, Bethesda, MA 20892, USA.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Dagur
authors.forename: Angélique
authors.initials: A
authors.lastname: Biancotto
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: H Nida
authors.initials: HN
authors.lastname: Sen
authors.forename: Michael
authors.initials: M
authors.lastname: Yao
authors.forename: Warren
authors.initials: W
authors.lastname: Strober
authors.forename: Robert B
authors.initials: RB
authors.lastname: Nussenblatt
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology; D051929:CD146 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D051929:CD146 Antigen; D016207:Cytokines; D020381:Interleukin-17; C497902:MCAM protein, human