Aim To investigate the effects of JAK inhibitor （SHR0302） on adjuvant-induced arthritis （AA） rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Thl7, Treg, tot...Aim To investigate the effects of JAK inhibitor （SHR0302） on adjuvant-induced arthritis （AA） rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Thl7, Treg, total B cells and memory B cells. Methods Animals were divided randomly into 6 groups including normal control, AA, SHR0302 （0.3, 1.0, 3.0 nag · kg^-1, ig） and MTX （0.5 nag · kg^-1 , ig） . The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen, inflammatory cytokine and antibody production in serum. We examined the proliferation of T, B and FLS by CCK8 kit; Thl7, Treg, total B and memory B cell proportion was measured by flow cytometry; Cytokines TNF-αβ, IL-1β, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by ELISA kits; The ex- pression of p-JAK1 and p-STAT3 was measured by Western blot analysis. Results SHR0302 suppressed the se- verity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and allevia- ted histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Thl7 and total B, and inhibited JAK1-STAT3 phosphorylation; There was no significant effect on Treg function and memory B cell proportion. Conclusion SHR0302 may attenuate the severity of AA rats, partially through signifi- cantly reducing Thl7 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation.展开更多
Background Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4^＋ T cells subsets might play a role in asthma. We investigated the relative abundance and activit...Background Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4^＋ T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells in patients with allergic asthma. Methods Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells were determined by flow cytometry. The expression of cytokines in plasma and Jn the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. Results The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4^＋CD25^＋ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Conclusions Imbalances in Thl/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.展开更多
Background Systemic sclerosis （SSc） is an autoimmune disease that has three major components： inflammation, fibrosis, and vasculopathy. T-helper 17 cell （Th17） and regulatory T cell （Treg） are considered to be ...Background Systemic sclerosis （SSc） is an autoimmune disease that has three major components： inflammation, fibrosis, and vasculopathy. T-helper 17 cell （Th17） and regulatory T cell （Treg） are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4＊CD25~ Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis. Methods Th17s （CD4 and IL-17 positive） and CD4＊CD25~ Tregs （CD4, CD25 and Foxp3 positive） in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score （MRSS）, anti-topoisomerase I antibody, anti-U1 ribonucleoprotein （RNP） antibody, systemic involvements, pulmonary function test （PFT） and high resolution computed tomography （HRCT） score were prospectively collected following EUSTAR （EULAR scleroderma trial and research group） protocols. The correlations between the experimental and clinical data were investigated. Results The ratio of Th17 in SSc patients was significantly elevated compared to healthy controls （8.74% vs. 4.41%, P 〈0.001）. The amount of Th17 was positively correlated with disease duration （R=-0.531, P=-0.013） and duration of the second symptoms （R=-0.505, P=0.023）. The ratio of CD4＊CD25＊ Treg in SSc patients also significantly differed from the healthy controls （3.04% vs. 2.24%, P=0.018）. Elevated Tregs were more frequently observed in patients with a high interstitial lung disease （ILD） score on computed tomography （24/36） compared with patients with normal ILD scores （4/12, ,P=-0.043）. Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity （DLCO） （24/34） compared with patients with normal DLCO （4/11, P=0.042）. Conclusions T cell abnormalities are remarkable in systemic sclerosis. Th17s proliferate and their numbers increase with lengthened disease duration. Th17s might participate in both inflammation and fibrosis by secreting IL-17. CD4＋CD25＋ Tress also proliferate in SSc and may play important roles in promoting fibrosis.展开更多
文摘Aim To investigate the effects of JAK inhibitor （SHR0302） on adjuvant-induced arthritis （AA） rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Thl7, Treg, total B cells and memory B cells. Methods Animals were divided randomly into 6 groups including normal control, AA, SHR0302 （0.3, 1.0, 3.0 nag · kg^-1, ig） and MTX （0.5 nag · kg^-1 , ig） . The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen, inflammatory cytokine and antibody production in serum. We examined the proliferation of T, B and FLS by CCK8 kit; Thl7, Treg, total B and memory B cell proportion was measured by flow cytometry; Cytokines TNF-αβ, IL-1β, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by ELISA kits; The ex- pression of p-JAK1 and p-STAT3 was measured by Western blot analysis. Results SHR0302 suppressed the se- verity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and allevia- ted histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Thl7 and total B, and inhibited JAK1-STAT3 phosphorylation; There was no significant effect on Treg function and memory B cell proportion. Conclusion SHR0302 may attenuate the severity of AA rats, partially through signifi- cantly reducing Thl7 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation.
文摘Background Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4^＋ T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells in patients with allergic asthma. Methods Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Thl, Th2, Th17 and CD4^＋CD25^＋ Treg cells were determined by flow cytometry. The expression of cytokines in plasma and Jn the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. Results The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4^＋CD25^＋ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Conclusions Imbalances in Thl/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.
文摘Background Systemic sclerosis （SSc） is an autoimmune disease that has three major components： inflammation, fibrosis, and vasculopathy. T-helper 17 cell （Th17） and regulatory T cell （Treg） are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4＊CD25~ Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis. Methods Th17s （CD4 and IL-17 positive） and CD4＊CD25~ Tregs （CD4, CD25 and Foxp3 positive） in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score （MRSS）, anti-topoisomerase I antibody, anti-U1 ribonucleoprotein （RNP） antibody, systemic involvements, pulmonary function test （PFT） and high resolution computed tomography （HRCT） score were prospectively collected following EUSTAR （EULAR scleroderma trial and research group） protocols. The correlations between the experimental and clinical data were investigated. Results The ratio of Th17 in SSc patients was significantly elevated compared to healthy controls （8.74% vs. 4.41%, P 〈0.001）. The amount of Th17 was positively correlated with disease duration （R=-0.531, P=-0.013） and duration of the second symptoms （R=-0.505, P=0.023）. The ratio of CD4＊CD25＊ Treg in SSc patients also significantly differed from the healthy controls （3.04% vs. 2.24%, P=0.018）. Elevated Tregs were more frequently observed in patients with a high interstitial lung disease （ILD） score on computed tomography （24/36） compared with patients with normal ILD scores （4/12, ,P=-0.043）. Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity （DLCO） （24/34） compared with patients with normal DLCO （4/11, P=0.042）. Conclusions T cell abnormalities are remarkable in systemic sclerosis. Th17s proliferate and their numbers increase with lengthened disease duration. Th17s might participate in both inflammation and fibrosis by secreting IL-17. CD4＋CD25＋ Tress also proliferate in SSc and may play important roles in promoting fibrosis.
