Constitutive STAT3 phosphorylation and IL-6/IL-10 co-expression are associated with impaired T-cell function in tuberculosis patients

作     者：Kirstin Harling Ernest Adankwah Alptekin Güler Anthony Afum-Adjei Awuah Louis Adu-Amoah Ertan Mayatepek Ellis Owusu-Dabo Norman Nausch Marc Jacobsen 

作者机构：Department of General PediatricsNeonatologyand Pediatric CardiologyUniversity Children’s HospitalDuesseldorf 40225Germany Kumasi Centre for collaborative Research in Tropical Medicine(KCCR)KumasiGhana School of Public HealthCollege of Health SciencesKwame Nkrumah University of Science and Technology(KNUST)KumasiGhana 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2019年第16卷第3期

页      面：275-287页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：by the German Research Foundation(DFG JA 1479/5-1)to N Nausch E.Owusu-Dabo and M.Jacobsen.K.Harling were supported by the‘Hedwig und Waldemar Hort Stipendienstiftung’.E.Adankwah and M.Jacobsen were supported by the Manchot graduate school‘Molecules of Infection(MOI)-3’ 

主　　题：tuberculosis Interleukin-6 Interleukin-10 STAT3 SOCS3 

摘      要：T-cells critically contribute to protection against Mycobacterium tuberculosis infection,and impaired T-cell responses can lead to disease ***-inflammatory and immunosuppressive cytokines affect T-cells,and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell *** STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune *** characterized blood samples from tuberculosis patients(n=28)and healthy contacts(n=28)from Ghana for ***-specific T-cell responses,constitutive cytokine production,and SOCS3 and pSTAT3 *** modulation of primary CD4+T-cells was performed to determine the effects of SOCS3 on T-cell functions.T-cells from tuberculosis patients expressed higher levels of IL-10 and IL-6 and lower levels of T helper type(TH)17 cytokines after ***-specific stimulation compared to healthy *** addition,tuberculosis patients had higher IL-10 and IL-6 levels in the supernatants of non-stimulated immune cells and plasma samples compared to healthy ***,aberrant cytokine expression was accompanied by high constitutive pSTAT3 levels and SOCS3 expression in *** analysis identified an IL-6/IL-10 co-expression-based principal component in tuberculosis patients that correlated with high pSTAT3 ***3 contributed to a regulatory component,and tuberculosis patients with high SOCS3 expression showed decreased TH1 cytokine expression and impaired IL-2-induced STAT5 ***3 over-expression in primary CD4+T-cells confirmed the SOCS3 inhibitory function on IL-2-induced STAT5 *** conclude that constitutive pSTAT3 and high SOCS3 expression are influential factors that indicate impaired T-cell functions in tuberculosis patients.