title: Slamf6 negatively regulates autoimmunity.
abstract: The nine SLAM family (Slamf) receptors are positive or negative regulators of adaptive and innate immune responses, and of several autoimmune diseases. Here we report that the transfer of Slamf6-/-B6 CD4+T cells into co-isogenic bm12 mice causes SLE-like autoimmunity with elevated levels of autoantibodies. In addition, significantly higher percentages of Tfh cells and IFN-γ-producing CD4+cells, as well as GC B cells were observed. Interestingly, the expression of the Slamf6-H1 isoform in Slamf6-/-CD4+T cells did not induce this lupus-like phenotype. By contrast, Slamf1-/-or Slamf5-/-CD4+T cells caused the same pathology as WT CD4+T cells. As the transfer of Slamf [1+6]-/-or Slamf [1+5+6]-/-CD4+T cells induced WT levels of autoantibodies, the presence of Slamf1 was requisite for the induction of increased levels of autoantibodies by Slamf6-/-CD4+T cells. We conclude that Slamf6 functions as an inhibitory receptor that controls autoimmune responses.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. Electronic address: nwang@bidmc.harvard.edu.
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Marton
authors.initials: M
authors.lastname: Keszei
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Halibozek
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Burcu
authors.initials: B
authors.lastname: Yigit
authors.affiliation: Department of Biomedical Sciences, Medical School, University of Barcelona, Barcelona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Engel
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. Electronic address: cterhors@bidmc.harvard.edu.
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008822:Mice, Transgenic; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000276:immunology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1 / Q000276:immunology
chemical_list: D001323:Autoantibodies; C498971:Cd84 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family; C000604062:Slamf1 protein, mouse; C000604063:Slamf6 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D007371:Interferon-gamma
keywords: Autoantibody; GVH; Slamf6; Tfh cells