Phosphorylated STAT3 and PD-1 regulate IL-17 production and IL-23 receptor expression in Mycobacterium tuberculosis infection.
Phosphorylated STAT3 and PD-1 regulate IL-17 production and IL-23 receptor expression in Mycobacterium tuberculosis infection.
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DOI：
10.1002/eji.201343680
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发表时间：
2014-07
影响因子：
5.4
通讯作者：
Valluri, Vijayalakshmi
中科院分区：
文献类型：
--
作者：
Bandaru, Anuradha;Devalraju, Kamakshi P.;Paidipally, Padmaja;Dhiman, Rohan;Venkatasubramanian, Sambasivan;Barnes, Peter F.;Vankayalapati, Ramakrishna;Valluri, Vijayalakshmi
我们研究了在人类结核感染中调节IL-23受体表达和IL-17产生的因素。结核分枝杆菌(M.TB)刺激的来自结核病患者的CD4+细胞分泌的IL-17比来自健康的结核菌素反应物(PPD+)的CD4+细胞少。结核分枝杆菌培养的单核细胞和PPD+供者培养的单核细胞表达等量的IL-23p19mRNA和蛋白，提示IL-23的产生减少不是结核病患者IL-17产生减少的原因。与PPD+捐献者相比，来自结核病患者的新鲜分离的和结核分枝杆菌刺激的CD4+细胞减少了IL-23受体和磷酸化STAT3(PSTAT3)的表达。STAT3 siRNA减少了PPD+供者的CD4+细胞IL-23受体的表达和IL-17的产生。与PPD+健康人相比，肺结核患者的PD-1+T细胞数量增加。抗PD-1抗体促进结核分枝杆菌培养的CD4+细胞pSTAT3和IL-23R的表达及IL-17的产生。抗结核治疗降低PD-1的表达，增加IL-17和干扰素-γ的产生，以及pSTAT3、IL-23R的表达。这些结果表明，PD-1表达增加，pSTAT3表达减少，结核病患者CD4+细胞IL-23受体表达和IL-17产生减少。
We studied the factors that regulate IL-23 receptor expression and IL-17 production in human tuberculosis infection. Mycobacterium tuberculosis (M. tb)-stimulated CD4+ cells from tuberculosis patients secreted less IL-17 than did CD4+ cells from healthy tuberculin reactors (PPD+). M. tb cultured monocytes from tuberculosis patients and PPD+ donors expressed equal amounts of IL-23p19 mRNA and protein, suggesting that reduced IL-23 production is not responsible for decreased IL-17 production by tuberculosis patients. Freshly isolated and M. tb- stimulated CD4+ cells from tuberculosis patients had reduced IL-23 receptor and phosphorylated STAT3 (pSTAT3) expression, compared to PPD+ donors. STAT3 siRNA reduced IL-23 receptor expression, and IL-17 production by CD4+ cells from PPD+ donors. Tuberculosis patients had increased number of PD-1+ T cells compared to healthy PPD+ individuals. Anti-PD-1 antibody enhanced pSTAT3 and IL-23R expression and IL-17 production by M. tb cultured CD4+ cells of tuberculosis patients. Anti-tuberculosis therapy decreased PD-1 expression, increased IL-17 and IFN-γ production and pSTAT3, IL-23R expression. These findings demonstrate that increased PD-1 expression and decreased pSTAT3 expression reduces IL-23 receptor expression and IL-17 production by CD4+ cells of tuberculosis patients.
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影响因子：
5.4
作者：
Garg, Ankita;Barnes, Peter F.;Vankayalapati, Ramakrishna
通讯作者：
Vankayalapati, Ramakrishna
影响因子：
20.3
作者：
de Wit, Jelle;Souwer, Yuri;van Ham, Marieke
通讯作者：
van Ham, Marieke
影响因子：
3.2
作者：
Marin, Nancy D.;Paris, Sara C.;Garcia, Luis F.
通讯作者：
Garcia, Luis F.
影响因子：
--
作者：
Kumar, N. Pavan;Anuradha, R.;Babu, Subash
通讯作者：
Babu, Subash
影响因子：
--
作者：
Marin, Nancy D.;Paris, Sara C.;Garcia, Luis F.
通讯作者：
Garcia, Luis F.