Myeloid cytokines distinctly and reversibly control LAIR-1 (CD305) expression on monocytes-mΦs/monocyte-DCs.

Cross-linking of the inhibitory immunoreceptor LAIR-1 (CD305) on the cell surface phosphorylates LAIR-1 inhibitory motifs (ITIM) and restricts the growth of monocyte-derived dendritic cells (mono-DCs). Despite the suggestion that LAIR-1’s ability to prevent unwarranted immunity is compromised in autoimmunity, much remains to be learned about the control of LAIR-1 expression. Here, we compared the ability of various myeloid cytokines to control LAIR-1 expression on the surface of monocytes/macrophages (mϕs) and mono-DCs. Treatment of freshly isolated blood monocytes from healthy donors with mono-DC growth factors (GM-CSF+IL-4/GM-CSF+IL-13) led to reduced levels of LAIR-1 at the critical monocyte-to-mono-DC juncture. In contrast, M-CSF (a steady state/M2 cytokine) sustained LAIR-1+CD14+CD33m/M+CD16+ mono-mϕs. M-CSF effects on LAIR-1 occurred under serum-supplemented and serum-free conditions. Addition of M-CSF to mono-DCs previously cultured in GM-CSF+IL-4 promptly reversed the down-regulatory effects of GM-CSF+IL-4 producing increases in LAIR-1+CD14+ cells. Conversely, addition of GM-CSF+IL-4 to M-CSF exposed cultures lowered levels of LAIR-1 and CD14. M-CSF treatment of SLE blood myeloid cells (featuring activated monocytes/mono-DCs lacking LAIR-1, CD14) produced high levels of LAIR-1 and CD14 vs GM-CSF/IL-4. Thus: 1. The expression of LAIR-1 on monocytes/mϕs and mono-DCs is distinctly and reversibly controlled by myeloid cytokines. 2. LAIR-1 expression on circulating myeloid cells in SLE may be regulated by M-CSF.