ABSTRACT
Interleukin-21 (IL-21) has broad actions on T and B cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive α-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive transfer of wild-type CD4+ T cells caused more severe colitis with increased DCs and interferon-γ (IFN-γ)-producing CD4+ T cells in Il21r(-/-)Rag2(-/-) mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2(-/-) mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response.
Subject(s)
Apoptosis/immunology , Dendritic Cells/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Interleukins/immunology , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/immunology , Apoptosis Regulatory Proteins/metabolism , Bcl-2-Like Protein 11 , Blotting, Western , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cells, Cultured , DNA, Intergenic/genetics , DNA, Intergenic/immunology , DNA, Intergenic/metabolism , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , DNA-Binding Proteins/immunology , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Flow Cytometry , Galactosylceramides/immunology , Galactosylceramides/pharmacology , Gene Expression/drug effects , Gene Expression/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukins/genetics , Interleukins/pharmacology , Membrane Proteins/genetics , Membrane Proteins/immunology , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Natural Killer T-Cells/drug effects , Natural Killer T-Cells/immunology , Natural Killer T-Cells/metabolism , Oligonucleotide Array Sequence Analysis , Protein Binding/immunology , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/immunology , Proto-Oncogene Proteins/metabolism , Receptors, Interleukin-21/deficiency , Receptors, Interleukin-21/genetics , Receptors, Interleukin-21/immunology , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/immunologyABSTRACT
Se presenta el caso de un paciente adulto mayor que acude a consulta por presentar astenia, anorexia, pérdida de peso y toma del estado general, así como dolor en el hipocondrio derecho con irradiación a epigastrio y lesiones hiperpigmentadas de la piel del tronco, miembros inferiores y superiores. Se evidenció en la biopsia de piel la presencia de acantosis nigricans, y se demostró posteriormente su carácter de síndrome paraneoplásico asociado con cáncer de estómago. Se discute la asociación entre acantosis nigricans y cáncer gástrico.
The case of an adult patient seen at the physician's office for presenting asthenia, anorexia, weight loss and malaise, as well as pain in the right hypochondrium irradating to epigastrium and hyperpigmented lesions of the trunk skin, lower and upper limbs, was presented. In the skin biopsy, it was evidenced the presence of acanthosis nigricans, and its paraneoplastic syndrome associated with stomach cancer was later proved. The connection between acanthosis nigricans and gastric cancer was discussed.