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1.
J Immunol ; 203(4): 911-921, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31235553

RESUMO

Th17 cells play a critical role in the adaptive immune response against extracellular bacteria, and the possible mechanisms by which they can protect against infection are of particular interest. In this study, we describe, to our knowledge, a novel IL-1ß dependent pathway for secretion of the antimicrobial peptide IL-26 from human Th17 cells that is independent of and more rapid than classical TCR activation. We find that IL-26 is secreted 3 hours after treating PBMCs with Mycobacterium leprae as compared with 48 hours for IFN-γ and IL-17A. IL-1ß was required for microbial ligand induction of IL-26 and was sufficient to stimulate IL-26 release from Th17 cells. Only IL-1RI+ Th17 cells responded to IL-1ß, inducing an NF-κB-regulated transcriptome. Finally, supernatants from IL-1ß-treated memory T cells killed Escherichia coli in an IL-26-dependent manner. These results identify a mechanism by which human IL-1RI+ "antimicrobial Th17 cells" can be rapidly activated by IL-1ß as part of the innate immune response to produce IL-26 to kill extracellular bacteria.


Assuntos
Imunidade Inata/imunologia , Interleucina-1beta/imunologia , Interleucinas/imunologia , Ativação Linfocitária/imunologia , Células Th17/imunologia , Infecções Bacterianas/imunologia , Humanos , Interleucina-1beta/metabolismo , Interleucinas/metabolismo , Células Th17/microbiologia
2.
Arch Dermatol Res ; 306(9): 793-801, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25018055

RESUMO

Leprosy is not only a bacteriological disease but also an immunological disease, in which T helper17 and CD4(+) CD25(high)FoxP3(+) regulatory T cells (T-regs), among others, may play a role. We aimed to evaluate serum levels of interleukin (IL)-17, IL-22 (Th17 cytokines), IL-10 and transforming growth factor (TGF)-ß (down regulatory cytokines) in 43 untreated leprosy patients and 40 controls by enzyme-linked immunosorbent assay, and to assess circulating CD4(+) CD25(high)FoxP3(+)T-regs in patients using flow cytometry. Patients were grouped into tuberculoid, pure neural, borderline, lepromatous, type 1 reactional leprosy, and erythema nodosum leprosum. IL-10 and TGF-ß were significantly higher in patients as compared to controls (p < 0.001), while IL-17, but not IL-22, was significantly lower (p < 0.001), with no significant difference comparing patients' subgroups. Significantly higher CD4(+) CD25(high)FoxP3(+)T-regs levels was detected in tuberculoid, type 1 reaction and pure neural leprosy, while the lowest levels in erythema nodosum leprosum (p < 0.001). TregsFoxP3 expression% was significantly lower in pure neural leprosy than other patients' subgroups (p < 0.05). T-regs/T-effs was lowest in erythema nodosum leprosum (p < 0.05). TGF-ß correlated negatively with TregsFoxP3 expression% and T-effs% (p = 0.009 and 0.018 respectively). Leprosy is associated with defective IL-17 and overproduction of IL-10 and TGF-ß. Tuberculoid, type 1 reaction and pure neural leprosy express significantly higher circulating T-regs, consistent with effector immune mechanisms activation, but with lower TregsFoxP3 expression (in pure neural leprosy). Erythema nodosum leprosum is characterized by deficient T-regs and increased TregsFoxP3 expression%. The present study pinpointed a potential role of Th17, CD4(+) CD25(high)FoxP3(+)T-regs, and probably CD4(+) CD25(+)IL-10(+) T regulatory cells 1 (Tr1), and Th3 in leprosy.


Assuntos
Citocinas/sangue , Fatores de Transcrição Forkhead/sangue , Subunidade alfa de Receptor de Interleucina-2/sangue , Hanseníase/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interleucina-10/sangue , Interleucina-17/sangue , Interleucinas/sangue , Hanseníase/sangue , Hanseníase/diagnóstico , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/microbiologia , Células Th17/microbiologia , Fator de Crescimento Transformador beta/sangue , Adulto Jovem , Interleucina 22
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