Slamf6 negatively regulates autoimmunity

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.