title: Engagement of NK receptor NKG2D, but not 2B4, results in self-reactive CD8+ T cells and autoimmune vitiligo.
abstract: In this study, we demonstrate that engagement of two different natural killer receptors (NKRs) can lead to contrasting effects in the development of self-reactive CD8+T cells and autoimmune vitiligo. Specifically, using a mouse model, we show that CD8+T-cell targeting of a melanocyte antigen, tyrosinase-related protein-1 (TRP-1) in combination with delivery of the NKG2D ligands (Rae-1ϵ or H60), results in strong CD8+T-cell responses against TRP-1 and in the development of autoimmune vitiligo. In contrast, targeting of TRP-1 in combination with delivery of CD48, the natural ligand for the NKR 2B4, leads to reduced formation of TRP-1-reactive CD8+T-cell responses and decreased development of vitiligo. These data indicate that autoimmune vitiligo is limited by insufficient signals, despite plentiful self-reactive T cells in the peripheral immune system. To our knowledge, this is the first experimental evidence supporting the role of NKRs in modulating CD8+T-cell autoimmune vitiligo. This study supports the utilization of NKR signaling as a therapeutic avenue toward prevention of vitiligo and other autoimmune diseases.
authors.affiliation: Department of Surgery, Committee on Immunology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zloza
authors.forename: Gretchen E
authors.initials: GE
authors.lastname: Lyons
authors.forename: Lukasz K
authors.initials: LK
authors.lastname: Chlewicki
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Kohlhapp
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: O'Sullivan
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Lacek
authors.forename: Tamson V
authors.initials: TV
authors.lastname: Moore
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jagoda
authors.forename: Vinay
authors.initials: V
authors.lastname: Kumar
authors.forename: José A
authors.initials: JA
authors.lastname: Guevara-Patiño
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D000071178:CD48 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D000071176:Signaling Lymphocytic Activation Molecule Family; D014820:Vitiligo / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000071178:CD48 Antigen; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D008024:Ligands; D050505:Mutant Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1