title: Phosphorylated STAT3 and PD-1 regulate IL-17 production and IL-23 receptor expression in Mycobacterium tuberculosis infection.
abstract: We studied the factors that regulate IL-23 receptor expression and IL-17 production in human tuberculosis infection. Mycobacterium tuberculosis (M. tb)-stimulated CD4(+) T cells from tuberculosis patients secreted less IL-17 than did CD4(+) T 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(+) T cells from tuberculosis patients had reduced IL-23 receptor and phosphorylated STAT3 (pSTAT3) expression, compared with cells from PPD(+) donors. STAT3 siRNA reduced IL-23 receptor expression and IL-17 production by CD4(+) T cells from PPD(+) donors. Tuberculosis patients had increased numbers of PD-1(+) T cells compared with healthy PPD(+) individuals. Anti-PD-1 antibody enhanced pSTAT3 and IL-23R expression and IL-17 production by M. tb-cultured CD4(+) T cells of tuberculosis patients. Anti-tuberculosis therapy decreased PD-1 expression, increased IL-17 and IFN-γ production and pSTAT3 and IL-23R expression. These findings demonstrate that increased PD-1 expression and decreased pSTAT3 expression reduce IL-23 receptor expression and IL-17 production by CD4(+) T cells of tuberculosis patients.
authors.affiliation: Blue Peter Research Center, LEPRA Society, Cherlapally, Hyderabad, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Bandaru
authors.forename: Kamakshi P
authors.initials: KP
authors.lastname: Devalraju
authors.forename: Padmaja
authors.initials: P
authors.lastname: Paidipally
authors.forename: Rohan
authors.initials: R
authors.lastname: Dhiman
authors.forename: Sambasivan
authors.initials: S
authors.lastname: Venkatasubramanian
authors.forename: Peter F
authors.initials: PF
authors.lastname: Barnes
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Vankayalapati
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Valluri
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000096:biosynthesis; D010766:Phosphorylation; D061026:Programmed Cell Death 1 Receptor / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis; D014376:Tuberculosis / Q000276:immunology*
chemical_list: C515500:IL23R protein, human; D020381:Interleukin-17; D053759:Interleukin-23; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D018123:Receptors, Interleukin; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: Cytokine; Human; IL-17; M. tuberculosis