title: Necroptosis of Dendritic Cells Promotes Activation of γδ T Cells.
abstract: γδ T cells function at the interface between innate and adaptive immunity and have well-demonstrated roles in response to infection, autoimmunity and tumors. A common characteristic of these seemingly disparate conditions may be cellular stress or death. However, the conditions under which ligands for γδ T cells are induced or exposed remain largely undefined. We observed that induction of necroptosis of murine or human dendritic cells (DC) by inhibition of caspase activity paradoxically augments their ability to activate γδ T cells. Furthermore, upregulation of the stabilizer of caspase-8 activity, c-FLIP, by IL-4, not only greatly reduced the susceptibility of DC to necroptosis, but also considerably decreased their ability to activate γδ T cells. Collectively, these findings suggest that the induction of necroptosis in DC upregulates or exposes the expression of γδ T cell ligands, and they support the view that γδ T cells function in the immune surveillance of cell stress.
authors.affiliation: Vermont Center for Immunology and Infectious Diseases, Department of Medicine, The University of Vermont College of Medicine, Burlington, Vt., USA.
authors.forename: Cheryl C
authors.initials: CC
authors.lastname: Collins
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bashant
authors.forename: Cuixia
authors.initials: C
authors.lastname: Erikson
authors.forename: Phyu Myat
authors.initials: PM
authors.lastname: Thwe
authors.forename: Karen A
authors.initials: KA
authors.lastname: Fortner
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Craig T
authors.initials: CT
authors.lastname: Morita
authors.forename: Ralph C
authors.initials: RC
authors.lastname: Budd
mesh_terms: D000818:Animals; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D009842:Oligopeptides / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506387:Cflar protein, mouse; D009842:Oligopeptides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; D015847:Interleukin-4; D020169:Caspases