title: TNF superfamily cytokines in the promotion of Th9 differentiation and immunopathology.
abstract: The tumor necrosis factor (TNF) receptors and their corresponding cytokine ligands have been implicated in many aspects of the biology of immune functions. TNF receptors have key roles during various stages of T cell homeostasis. Many of them can co-stimulate lymphocyte proliferation and cytokine production. Additionally, several TNF cytokines can regulate T cell differentiation, including promoting Th1, Th2, Th17, and more recently the newly described Th9 subset. Four TNF family cytokines have been identified as regulators for IL-9 production by T cells. OX40L, TL1A, and GITRL can promote Th9 formation but can also divert iTreg into Th9, while 4-1BBL seems to inhibit IL-9 production from iTreg and has not been studied for its ability to promote Th9 generation. Regulation of IL-9 production by TNF family cytokines has repercussions in vivo, including enhancement of anti-tumor immunity and immunopathology in allergic lung and ocular inflammation. Regulating T cell production of IL-9 through blockade or agonism of TNF family cytokine receptors may be a therapeutic strategy for autoimmune and allergic diseases and in tumor.
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, MD, 20892, USA. meylanf@mail.nih.gov.
authors.forename: Françoise
authors.identifier: 0000-0002-9279-7875
authors.initials: F
authors.lastname: Meylan
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Siegel
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D055808:Drug Discovery; D006801:Humans; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D005810:Multigene Family; D011485:Protein Binding; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D016906:Interleukin-9; D048069:Tumor Necrosis Factors
keywords: Lung inflammation; TNF superfamily cytokines; Th9; Tumor immunology