RNA sequencing of bone marrow WT and SLAMF9-/- pDCs

SLAMF9 belongs to the conserved lymphocytic activation molecule family (SLAMF). Unlike other SLAMs, which have been extensively studied, the role of SLAMF9 in the immune system remained mostly unexplored. By generating CRISPR/CAS9 SLAMF9 knockout mice, we analyzed the role of this receptor in plasmacytoid dendritic cells (pDCs), which preferentially express the SLAMF9 transcript and protein. These cells display a unique capacity to produce type I interferon and bridge between innate and adaptive immune response. Analysis of pDCs in SLAMF9-/- mice revealed an increase of immature pDCs in the BM and enhanced accumulation of pDCs in the lymph nodes. In the periphery, SLAMF9 deficiency resulted in lower levels of the transcription factor SPIB, elevation of pDC survival, and attenuated IFN??and TNF??production. To define the role of SLAMF9 during inflammation, pDCs lacking SLAMF9 were followed during induced experimental autoimmune encephalomyelitis (EAE). SLAMF9-/- mice demonstrated attenuated disease and delayed onset, accompanied by a prominent increase of immature pDCs in the LN, with a reduced co-stimulatory potential and enhanced infiltration of pDCs into the central nervous system (CNS). These results suggest the crucial role of SLAMF9 in pDC differentiation, homeostasis and function in the steady state and during EAE. Overall design: Comparing the transcriptom of pDCs derived from WT and SLAMF9-/- mice