Abstract
Relapsing polychondritis (RP) is an inflammatory disease of unknown causes, characterized by recurrent inflammation in cartilaginous tissues of the whole body. Recently, researchers have reported that, in mouse experiments, altered gut microbe-dependent T cell differentiation occurred in gut associated lymphoid tissues. Here, we investigated whether gut microbe alteration existed, and if so, the alteration affected peripheral T cell differentiation in patients with RP. In an analysis of gut microbiota, we found increased annotated species numbers in RP patients compared with normal individuals. In the RP gut microbiota, we observed several predominant species, namely Veillonella parvula, Bacteroides eggerthii, Bacteroides fragilis, Ruminococcus bromii, and Eubacterium dolichum, all species of which were reported to associate with propionate production in human intestine. Propionate is a short-chain fatty acid and is suggested to associate with interleukin (IL)10-producing regulatory T (Treg) cell differentiation in gut associated lymphoid tissues. IL10 gene expressions were moderately higher in freshly isolated peripheral blood mononuclear cells (PBMC) of RP patients than those of normal individuals. Six hours after the initiation of the cell culture, regardless of the presence and absence of mitogen stimulation, IL10 gene expressions were significantly lower in RP patients than those in normal individuals. It is well known that PBMC of patients with autoimmune and inflammatory diseases show hyporesponsiveness to mitogen stimulation. We suggest that, in RP patients, continuous stimulation of intestinal T cells by excessive propionate leads to the spontaneous IL10 production and a subsequent refractory period of T cells in patients with RP. The hyporesponsiveness of Treg cells upon activation may associate with inflammatory cytokine production of PBMC and subsequently relate to chondritis in RP patients.
Highlights
Relapsing polychondritis (RP) is an uncommon systemic connective tissue disorder characterized by recurrent and episodic inflammation of cartilaginous tissues, such as ear, nose, joint, and respiratory tract [1]
We analyzed the feces of 25 RP patients and 27 normal individuals to obtain 16S rRNA metagenomic data
We compared the data of RP patients with those of age- and gender-matched normal individuals
Summary
Relapsing polychondritis (RP) is an uncommon systemic connective tissue disorder characterized by recurrent and episodic inflammation of cartilaginous tissues, such as ear, nose, joint, and respiratory tract [1]. RP often affects other proteoglycan rich organs, namely eye, inner ear, heart, blood vessels, and kidney [1]. The initial investigation of autoantibodies against type II collagen reported that the recognition manners to the antigens were disease (RP)-specific and the serum levels were correlated with disease severity [3]. Autoantibodies to matrilin, another cartilage protein, were observed in RP patients and had affinity to tracheolaryngeal and nasal cartilage [4]
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