RESUMO
Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T(H)-17 cells) share a developmental relationship with Foxp3(+) regulatory T cells (T(reg) cells). Here we show that a T(H)-17 population differentiates in the thymus in a manner influenced by recognition of self antigen and by the cytokines IL-6 and transforming growth factor-beta (TGF-beta). Like previously described T(H)-17 cells, the T(H)-17 cells that developed in the thymus expressed the transcription factor RORgamma t and the IL-23 receptor. These cells also expressed alpha(4)beta(1) integrins and the chemokine receptor CCR6 and were recruited to the lung, gut and liver. In the liver, these cells secreted IL-22 in response to self antigen and mediated host protection during inflammation. Thus, T(H)-17 cells, like T(reg) cells, can be selected by self antigens in the thymus.
Assuntos
Autoantígenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Interleucina-17/metabolismo , Subpopulações de Linfócitos T/imunologia , Timo/citologia , Animais , Linfócitos T CD4-Positivos/citologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Inflamação/imunologia , Integrina alfa4beta1/biossíntese , Interleucina-23/biossíntese , Interleucina-6/imunologia , Interleucina-6/metabolismo , Interleucinas/metabolismo , Camundongos , Camundongos Transgênicos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Reação em Cadeia da Polimerase , Receptores CCR6/biossíntese , Receptores do Ácido Retinoico/biossíntese , Receptores dos Hormônios Tireóideos/biossíntese , Subpopulações de Linfócitos T/citologia , Timo/imunologia , Fator de Crescimento Transformador beta/imunologia , Fator de Crescimento Transformador beta/metabolismo , Interleucina 22RESUMO
CD4+ T(H)17 cells display a featured role in barrier immunity. This effector population of T cells is important for clearance of microorganisms but can also promote autoimmunity at barrier sites. Recent work has indicated that these effector cells share a pathway with CD4+ regulatory T cells (T(R) cells) that also have a critical function in barrier protection and immune regulation. The development and function of T(H)17 cells, and their relationship with T(R) cells are discussed.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Trato Gastrointestinal/imunologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Pulmão/imunologia , Pele/imunologia , Animais , Doenças Autoimunes/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Diferenciação Celular , Trato Gastrointestinal/patologia , Humanos , Imunidade Celular , Imunidade nas Mucosas , Infecções/imunologia , Interleucina-17/química , Pulmão/patologia , Transdução de Sinais , Pele/patologia , Linfócitos T Reguladores/imunologia , Ativação TranscricionalRESUMO
The role of specialized follicular helper T (T(FH)) cells in the germinal center has become well recognized, but it is less clear how effector T cells govern the extrafollicular response, the dominant pathway of high-affinity, isotype-switched autoantibody production in the MRL/MpJ-Fas(lpr) (MRL(lpr)) mouse model of lupus. MRL(lpr) mice lacking the Icos gene have impaired extrafollicular differentiation of immunoglobulin (Ig) G(+) plasma cells accompanied by defects in CXC chemokine receptor (CXCR) 4 expression, interleukin (IL) 21 secretion, and B cell helper function in CD4 T cells. These phenotypes reflect the selective loss of a population of T cells marked by down-regulation of P-selectin glycoprotein ligand 1 (PSGL-1; also known as CD162). PSGL-1(lo) T cells from MRL(lpr) mice express CXCR4, localize to extrafollicular sites, and uniquely mediate IgG production through IL-21 and CD40L. In other autoimmune strains, PSGL-1(lo) T cells are also abundant but may exhibit either a follicular or extrafollicular phenotype. Our findings define an anatomically distinct extrafollicular population of cells that regulates plasma cell differentiation in chronic autoimmunity, indicating that specialized humoral effector T cells akin to T(FH) cells can occur outside the follicle.