Chitinase 3-like-1 is produced by human Th17 cells and correlates with the level of inflammation in juvenile idiopathic arthritis patients.
BACKGROUND
CHI3L1 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.


METHODS
A 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.


RESULTS
At 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.


CONCLUSIONS
Here 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.
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Manuela
M
Capone
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Laura
L
Maggi
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Veronica
V
Santarlasci
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Maria Caterina
MC
Rossi
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Alessio
A
Mazzoni
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Gianni
G
Montaini
Anna Meyer Children's Hospital and University of Florence, 50134, Florence, Italy.
Rolando
R
Cimaz
Dept. of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.
Matteo
M
Ramazzotti
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Marie Pierre
MP
Piccinni
Dept. of Clinical & Experimental Medicine, Second University of Naples, 80131 Naples, Italy.
Giusi
G
Barra
Dept. of Clinical & Experimental Medicine, Second University of Naples, 80131 Naples, Italy ; Institute of Protein Biochemistry, CNR, 80131, Naples, Italy.
Raffaele
R
De Palma
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Francesco
F
Liotta
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Enrico
E
Maggi
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Sergio
S
Romagnani
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy ; Department of Internal Medicine, University of Florence, Viale Pieraccini 6, 50134 Florence, Italy.
Francesco
F
Annunziato
Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence, 50134 Florence, Italy.
Lorenzo
L
Cosmi
CD161; CHI3L1; CRP; JIA; SF; Th17 cells