title: Promoting immune responses by LIGHT in the face of abundant regulatory T cell inhibition.
abstract: CD4(+) regulatory T cell (Treg) populations are believed to play very important roles in the suppression of immune responses. Overriding Treg inhibition is necessary for initiating primary immune reaction upon inflammatory Ag stimulation. LIGHT, TNF superfamily member 14, has been shown to be a costimulatory molecule for effector T cells. Overexpression of lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) on T cells induces strong T cell-mediated experimental intestinal inflammation. How this process is initiated by LIGHT in suppressive intestinal environments remains incompletely understood. In this study, we assessed the effect of LIGHT on Tregs. Our results indicate that LIGHT can support the expansion and function of Tregs. However, when LIGHT was highly expressed, these abundant Tregs failed to suppress the development of T cell-mediated experimental colitis and antitumor immunity. We showed that this might be, in part, due to an ability of LIGHT to promote effector T cell proliferation and differentiation even in a Treg-abundant environment. Our data collectively suggest that LIGHT might be a critical cytokine involved in the development of autoimmune inflammatory diseases and that LIGHT-targeted immunotherapy might be useful in the treatment of these diseases.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA. yugang@uchicago.edu
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D007165:Immunosuppression Therapy / Q000379:methods; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; C064658:RAG-1 protein