title: IL-9 Expression by Invariant NKT Cells Is Not Imprinted during Thymic Development.
abstract: Invariant NKT (iNKT) cell thymic development can lead to distinct committed effector lineages, namely NKT1, NKT2, and NKT17. However, following identification of IL-9-producing iNKT cells involved in mucosal inflammation, their development remains unaddressed. In this study, we report that although thymic iNKT cells from naive mice do not express IL-9, iNKT cell activation in the presence of TGF-β and IL-4 induces IL-9 secretion in murine and human iNKT cells. Acquisition of IL-9 production was observed in different iNKT subsets defined by CD4, NK1.1, and neuropilin-1, indicating that distinct functional subpopulations are receptive to IL-9 polarization. Transcription factor expression kinetics suggest that regulatory mechanisms of IL-9 expression are shared by iNKT and CD4 T cells, with Irf4 and Batf deficiency deeply affecting IL-9 production. Importantly, adoptive transfer of an enriched IL-9(+) iNKT cell population leads to exacerbated allergic inflammation in the airways upon intranasal immunization with house dust mite, confirming the ability of IL-9-producing iNKT cells to mediate proinflammatory effects in vivo, as previously reported. Taken together, our data show that peripheral iNKT cells retain the capacity of shaping their function in response to environmental cues, namely TGF-β and IL-4, adopting an IL-9-producing NKT cell phenotype able to mediate proinflammatory effects in vivo, namely granulocyte and mast cell recruitment to the lungs.
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; and Instituto Gulbenkian de Ciencia, 2780-156 Oeiras, Portugal.
authors: Marta
authors: M
authors: Monteiro
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; and Instituto Gulbenkian de Ciencia, 2780-156 Oeiras, Portugal.
authors: Ana
authors: A
authors: Agua-Doce
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; and Instituto Gulbenkian de Ciencia, 2780-156 Oeiras, Portugal.
authors: Catarina F
authors: CF
authors: Almeida
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; and.
authors: Diogo
authors: D
authors: Fonseca-Pereira
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; and.
authors: Henrique
authors: H
authors: Veiga-Fernandes
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; and Instituto Gulbenkian de Ciencia, 2780-156 Oeiras, Portugal lgraca@fm.ul.pt.
authors: Luis
authors: L
authors: Graca
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000235:genetics; D015847:Interleukin-4 / Q000276:immunology*; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000637:transplantation; D039942:Neuropilin-1 / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D000950:Antigens, Ly; D050976:Basic-Leucine Zipper Transcription Factors; D015704:CD4 Antigens; D050835:Interferon Regulatory Factors; D015847:Interleukin-4; D016906:Interleukin-9; D055651:NK Cell Lectin-Like Receptor Subfamily B; D039942:Neuropilin-1; D016212:Transforming Growth Factor beta; D000099218:Interferon Regulatory Factor-4; C431772:Batf protein, mouse; C527211:Klrb1c protein, mouse