title: Cutting edge: an NK cell-independent role for Slamf4 in controlling humoral autoimmunity.
abstract: Several genes within a syntenic region of human and mouse chromosome 1 are associated with predisposition to systemic lupus erythematosus. Analyses of lupus-prone congenic mice have pointed to an important role for the signaling lymphocyte activation molecule family (slamf)6 surface receptor in lupus pathogenesis. In this article, we demonstrate that a second member of the Slamf gene family, Slamf4 (Cd244), contributes to lupus-related autoimmunity. B6.Slamf4(-/-) mice spontaneously develop activated CD4 T cells and B cells and increased numbers of T follicular helper cells and a proportion develop autoantibodies to nuclear Ags. B6.Slamf4(-/-) mice also exhibit markedly increased autoantibody production in the B6.C-H-2bm12/KhEg → B6 transfer model of lupus. Although slamf4 function is best characterized in NK cells, the enhanced humoral autoimmunity of B6.Slamf4(-/-) mice is NK cell independent, as judged by depletion studies. Taken together, our findings reveal that slamf4 has an NK cell-independent negative regulatory role in the pathogenesis of lupus a normally non-autoimmune prone genetic background.
authors.affiliation: Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Brown
authors.forename: Silvia
authors.initials: S
authors.lastname: Calpe
authors.forename: Marton
authors.initials: M
authors.lastname: Keszei
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.forename: Shannon
authors.initials: S
authors.lastname: McArdel
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001323:Autoantibodies / Q000096:biosynthesis*; D002843:Chromatin / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; C490007:Cd244a protein, mouse; D002843:Chromatin; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family