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1.
Cell Rep ; 38(2): 110209, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35021099

RESUMO

Innate-like T cells, including invariant natural killer T cells, mucosal-associated invariant T cells, and γδ T cells, are present in various barrier tissues, including the lung, where they carry out protective responses during infections. Here, we investigate their roles during pulmonary pneumococcal infection. Following infection, innate-like T cells rapidly increase in lung tissue, in part through recruitment, but T cell antigen receptor activation and cytokine production occur mostly in interleukin-17-producing NKT17 and γδ T cells. NKT17 cells are preferentially located within lung tissue prior to infection, as are CD103+ dendritic cells, which are important both for antigen presentation to NKT17 cells and γδ T cell activation. Whereas interleukin-17-producing γδ T cells are numerous, granulocyte-macrophage colony-stimulating factor is exclusive to NKT17 cells and is required for optimal protection. These studies demonstrate how particular cellular interactions and responses of functional subsets of innate-like T cells contribute to protection from pathogenic lung infection.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Animais , Linhagem Celular , Células Dendríticas/imunologia , Feminino , Humanos , Interferon gama/imunologia , Interleucina-17/imunologia , Linfócitos Intraepiteliais/imunologia , Linfócitos Intraepiteliais/metabolismo , Pulmão/imunologia , Pulmão/microbiologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções Pneumocócicas/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Streptococcus pneumoniae/imunologia
2.
Nat Commun ; 12(1): 1446, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664261

RESUMO

Invariant natural killer T cells (iNKT cells) differentiate into thymic and peripheral NKT1, NKT2 and NKT17 subsets. Here we use RNA-seq and ATAC-seq analyses and show iNKT subsets are similar, regardless of tissue location. Lung iNKT cell subsets possess the most distinct location-specific features, shared with other innate lymphocytes in the lung, possibly consistent with increased activation. Following antigenic stimulation, iNKT cells undergo chromatin and transcriptional changes delineating two populations: one similar to follicular helper T cells and the other NK or effector like. Phenotypic analysis indicates these changes are observed long-term, suggesting that iNKT cells gene programs are not fixed, but they are capable of chromatin remodeling after antigen to give rise to additional subsets.


Assuntos
Pulmão/citologia , Células T Matadoras Naturais/citologia , Células T Auxiliares Foliculares/citologia , Subpopulações de Linfócitos T/citologia , Timo/citologia , Animais , Diferenciação Celular/imunologia , Cromatina/genética , Feminino , Pulmão/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células T Matadoras Naturais/imunologia , Células T Auxiliares Foliculares/imunologia , Subpopulações de Linfócitos T/imunologia , Timo/imunologia , Transcriptoma/genética
3.
Mucosal Immunol ; 14(3): 679-690, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33568785

RESUMO

Inflammatory bowel disease is characterized by an exacerbated intestinal immune response, but the critical mechanisms regulating immune activation remain incompletely understood. We previously reported that the TNF-superfamily molecule TNFSF14 (LIGHT) is required for preventing severe disease in mouse models of colitis. In addition, deletion of lymphotoxin beta receptor (LTßR), which binds LIGHT, also led to aggravated colitis pathogenesis. Here, we aimed to determine the cell type(s) requiring LTßR and the mechanism critical for exacerbation of colitis. Specific deletion of LTßR in neutrophils (LTßRΔN), but not in several other cell types, was sufficient to induce aggravated colitis and colonic neutrophil accumulation. Mechanistically, RNA-Seq analysis revealed LIGHT-induced suppression of cellular metabolism, and mitochondrial function, that was dependent on LTßR. Functional studies confirmed increased mitochondrial mass and activity, associated with excessive mitochondrial ROS production and elevated glycolysis at steady-state and during colitis. Targeting these metabolic changes rescued exacerbated disease severity. Our results demonstrate that LIGHT signals to LTßR on neutrophils to suppress metabolic activation and thereby prevents exacerbated immune pathogenesis during colitis.


Assuntos
Colite/imunologia , Doenças Inflamatórias Intestinais/imunologia , Receptor beta de Linfotoxina/metabolismo , Mitocôndrias/metabolismo , Neutrófilos/metabolismo , Ativação Metabólica , Animais , Sulfato de Dextrana , Modelos Animais de Doenças , Progressão da Doença , Humanos , Receptor beta de Linfotoxina/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/imunologia , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
4.
Cell Stem Cell ; 25(4): 454-455, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31585091

RESUMO

Invariant natural killer T (iNKT) cells have been tested for their potential use in cancer immune therapy, but their low frequency has limited their use. In this issue, Zhu and colleagues propose to overcome this by engineering hematopoietic stem cells (HSCs) to provide a continual source of iNKT cells. (Zhu et al., 2019).


Assuntos
Células T Matadoras Naturais , Neoplasias , Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco
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