Chitinase 3-like-1 is produced by human Th17 cells and correlates with the level of inflammation in juvenile idiopathic arthritis patients

Abstract

BackgroundCHI3L1 is a chitinase-like protein without enzymatic activity, produced by activated macrophages, chondrocytes, neutrophils. Recent studies on arthritis, asthma, and inflammatory bowel diseases suggest that chitinases are important in inflammatory processes and tissue remodeling, but their production by human T cells, has never been reported.MethodsA microarray analysis of gene expression profile was performed on Th17 and classic Th1 cell clones and CHI3L1 was found among the up-regulated genes on Th17 cells. Different types of helper T cell clones (TCCs) were then evaluated by Real Time PCR (RT-PCR) for CHI3L1 mRNA expression; protein expression was investigated in cell lysates by western blotting and in cultures supernatants by ELISA. ELISA was also used to measure CHI3L1 in the serum and in the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients.ResultsAt mRNA level CHI3L1 was highly expressed by Th17, Th17/Th1, non classic Th1 and even in Th17/Th2 cell clones, whereas it was virtually absent in CD161− classic Th1 and Th2 TCCs. CHI3L1 was also detected in cell culture supernatants of Th17 and Th17-derived cells but not of classic Th1. Moreover CHI3L1 was higher in the SF than in serum of JIA patients, and it positively correlated with the frequency of Th17 and non-classic Th1 cells in SF. CHI3L1 in SF also positively correlated with the C reactive protein (CRP) serum levels, and with the levels of some proinflammatory cytokines, such as IL-6 and p40, which is the common subunit of IL12 and IL23.ConclusionsHere we describe for the first time CHI3L1 production by T cells owing the Th17 family. Moreover the positive correlation found between the frequency of Th17 and Th17-derived cell subsets and CHI3L1 levels in SF of JIA patients, in agreement with the suggested role of these cells in inflammatory process, candidates CHI3L1 as a possible biological target in JIA treatment.

Altered Fc galactosylation in IgG4is a potential serum marker for chronic lung disease

“…Periostin is a potential diagnostic target in asthma [ 28 ], and CHI3L has been suggested as an airway inflammation and remodelling marker in both SA and pulmonary sarcoidosis [ 17 , 29 , 30 ]. Interestingly, CHI3L is produced by Th17 cells [ 31 ], which can be active both in sarcoidosis and SA. Furthermore, Th17 cells have been shown to regulate IgG sialylation in antibody-producing plasma cells [ 32 ].…”

Th17 and Th1 Lymphocytes in Oligoarticular Juvenile Idiopathic Arthritis

“…Additional evidence of the pathogenic features of CD4+CD161+ T cells, including pure Th17 cells and their derivative phenotypes Th17/Th1 and non-classic Th1, derived from a recent paper ( 44 ), describing that all these subsets express CHI3L1. This chitinase-like protein without enzymatic activity is defined in the literature as a well-known marker of disease activity and inflammation in several immune-mediated disorders ( 44 – 47 ): its levels are elevated in SF of children affected by oligoarticular JIA and positively correlated to inflammatory parameters ( 44 ).…”

Mesenchymal stem cells alleviate experimental immune-mediated liver injury via chitinase 3-like protein 1-mediated T cell suppression

“…Chitinase-3-like protein 1 (CHI3L1), a highly evolutionarily conserved secreted protein, have an important role in the pathogenesis of inflammatory diseases because of its upregulation in inflamed tissues of ulcerative colitis, Crohn's disease, rheumatoid arthritis, osteoarthritis and liver cirrhosis, as well as in solid cancers [6][7][8][9] . Elevated CHI3L1 expression plays a major role in microenvironment remodelling in different diseases 10 .…”