Abstract
Expression of the adhesion molecule, CD146/MCAM/MelCAM, on T cells has been associated with recent activation, memory subsets and T helper type 17 (Th17) effector function, and is elevated in inflammatory arthritis. Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA) and spondyloarthritides (SpA). Here, we compared the expression of CD146 on CD4+ T cells between healthy donors (HD) and patients with RA and SpA [ankylosing spondylitis (AS) or psoriatic arthritis (PsA)] and examined correlations with surface markers and cytokine secretion. Peripheral blood mononuclear cells (PBMC) were obtained from patients and controls, and synovial fluid mononuclear cells (SFMC) from patients. Cytokine production [elicited by phorbol myristate acetate (PMA)/ionomycin] and surface phenotypes were evaluated by flow cytometry. CD146+CD4+ and interleukin (IL)-17+CD4+ T cell frequencies were increased in PBMC of PsA patients, compared with HD, and in SFMC compared with PBMC. CD146+CD4+ T cells were enriched for secretion of IL-17 [alone or with IL-22 or interferon (IFN)-γ] and for some putative Th17-associated surface markers (CD161 and CCR6), but not others (CD26 and IL-23 receptor). CD4+ T cells producing IL-22 or IFN-γ without IL-17 were also present in the CD146+ subset, although their enrichment was less marked. Moreover, a majority of cells secreting these cytokines lacked CD146. Thus, CD146 is not a sensitive or specific marker of Th17 cells, but rather correlates with heterogeneous cytokine secretion by subsets of CD4+ helper T cells.
Highlights
Interleukin (IL)-17-secreting T helper type 17 (Th17) cells produce a distinct set of proinflammatory cytokines, including IL-17A, IL-17F and IL-21, which normally regulate immunity at intestinal barriers and enable defence against extracellular bacteria and fungi [1]
In order to quantify CD146 expression by CD4 T cells, Peripheral blood mononuclear cells (PBMC) were isolated from patients with rheumatoid arthritis (RA) or SpA and from healthy controls, and cryopreserved
CD3+CD4+ cells were identified within a lymphocyte scatter gate (Fig. 1a) and the percentage of CD146+ cells determined within this population (Fig. 1b)
Summary
Interleukin (IL)-17-secreting T helper type 17 (Th17) cells produce a distinct set of proinflammatory cytokines, including IL-17A, IL-17F and IL-21, which normally regulate immunity at intestinal barriers and enable defence against extracellular bacteria and fungi [1]. Th17 cells differentiate from naive CD4+ T cells under the combined control of proinflammatory myeloid- and tissue-derived cytokines, such as IL-1, IL-6, transforming growth factor (TGF)-β and/or IL-23. They express characteristic surface markers, such as the chemokine receptors, CCR6 and CCR4, the receptor for IL-23 and CD161 [2,3]. Th17 cells have been implicated in a wide range of autoimmune and inflammatory diseases [4]. Evidence for their importance in pathogenesis comes from gene ablation and cell transfer studies in animal models, genomewide association studies and phenotypical and functional analysis of patients’ T cells. Among rheumatological conditions with a recognized Th17 component are rheumatoid arthritis (RA) and the spondyloarthritides (SpAs), a group of related conditions including ankylosing spondylitis (AS), psoriatic arthritis (PsA), arthritis related to inflammatory bowel disease, reactive arthritis and a subgroup of juvenile idiopathic arthritis
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