Percentage of Th2 (b), Th9 (c) and Th17 (d) cells in SSc and HD. anti\systemic scleroderma 70 (Scl70) production by B cells. Our findings suggest that Th9 (Glp1)-Apelin-13 cells and IL\9 could be implicated in the pathogenesis of SSc. diffuse SSc02??005) (Fig. ?(Fig.3a,c)3a,c) and Th17 (12??03 033??008) (Fig. ?(Fig.3d)3d) cells was significantly higher in SSc patients respect to controls. Conversely, the percentage of IL\9\generating Th2 (04??009 02??003) cells was not significantly different in the two groups (Fig. ?(Fig.3b).3b). Interestingly, frequencies of Th9 cells were significantly higher in patients with diffuse SSc and the number of IL\9\expressing cells was correlated significantly with the altered Rodnan skin score, but not with pulmonary hypertension (Fig. ?(Fig.3eCg).3eCg). These findings show the presence of a (Glp1)-Apelin-13 Th9 polarization in the peripheral blood of SSc patients. Open in a separate window Physique 3 Percentage of T helper type 9 (Th9), Th17 and Th2 in systemic sclerosis (SSc) and healthy donors (HD). Representative dot\plot analysis and gating strategy in an SSc patient (a). Percentage of Th2 (b), Th9 (c) and Th17 (d) cells in SSc and HD. Mean percentage of Th9 cells in patients with diffuse or limited disease (e). Direct correlation of Th9 percentage in SSc and pulmonary hypertension (f) and Rodnan skin score (g). Data are expressed as mean??standard error of the mean (s.e.m.). [Colour figure can be viewed at wileyonlinelibrary.com] Innate lymphoid cells type 2 (ILC2) are expanded in the skin and peripheral blood of SSc Th9\derived IL\9 has been demonstrated to activate ILC2 in a mast cell\dependent manner 16. Furthermore, ILC2 have been described to be expanded in SSc patients 17. Thus, we next evaluated the frequencies of Th2 polarized ILC2 subsets in the skin and peripheral blood of SSc patients (Fig. ?(Fig.4).4). According to a previous report, ILC2 were expanded significantly in peripheral blood (Fig. ?(Fig.4a,b),4a,b), and cells resembling the ILC2 phenotype were also increased in the skin (Fig. ?(Fig.4c)4c) of SSc patients compared to controls. A significant and direct correlation was also found between the percentages of circulating ILC2 and Th9 cells (Fig. ?(Fig.44g). Open in a separate window Physique 4 Innate lymphoid cells (ILC) type 2 are expanded in systemic sclerosis (SSc) patients. Representative dot\plot analysis and gating strategy in a SSc patient (a). Mean percentage of ILC2 cells among peripheral blood mononuclear cells (PBMC) of patients and HD (b). Single staining for chemoattractant receptor Th2 (CRTH2) (c), GATA binding protein 3 (GATA3) (d) and interleukin (IL)\4 (e). (f) Merged triple staining for CRTH2, GATA3 and IL\4. ILC2 are directly correlated with Th9 (g). Data are expressed as mean??standard error of the mean (s.e.m.); *culture with recombinant IL\9 (b). Anti\systemic scleroderma 70 (Scl70) production after activation of B lymphocytes with recombinant IL\9 (c). [Colour figure can be viewed at wileyonlinelibrary.com] Conversation In this study we show, for the first time, that this IL\9/IL\9R axis is up\regulated in the inflamed skin of SSc patients and is accompanied by the growth of pathogenic Th9 cells. We also exhibited that Th9 polarization occurs in inflamed skin and in the peripheral blood of SSc patients, being correlated directly with the altered Rodnan skin score but not with pulmonary hypertension. Similar to the skin, IL\9 expression Rabbit Polyclonal to COX7S was also found increased in renal biopsy specimens of SSc patients with renal crisis. Finally, treatment with rIL\9 was associated with a significant induction of NETosis in neutrophils, significantly increased production of SSc\related autoantibodies by B lymphocytes and the growth of MC. IL\9 is usually a recently explained proinflammatory cytokine because of its capacity to support proliferation of B and T cell infiltration 20. In combination with IL\17, IL\9 increases the accumulation of neutrophils and perpetuates chronic inflammation 21, as observed in several autoimmune disorders such as rheumatoid arthritis (Glp1)-Apelin-13 (RA), psoriatic arthritis and giant cell arteritis (GCA) 22. IL\9 production was associated first with the Th2 phenotype, even if other T helper subsets appear to have the potential for IL\9 production such (Glp1)-Apelin-13 as Th17 cells and regulatory T cells (Treg) 23, 24. More recently, it has been exhibited that Th0 can differentiate into a specialized subset of IL\9\generating T cells, named Th9. Th9 differentiation and.
