A balance between KARAP/DAP12- and IRF-8/ICSBP–dependent signals governs the tolerogenic DC potential. Cell-surface receptors that noncovalently associate with KARAP/DAP12 on DCs are indicated. h indicates human; m, mouse; Siglec H, Sialic acid–binding Ig-like lectin H; MAIR-II, myeloid-associated immunoglobulin-like receptor II; PIRL-β, paired immunoglobulin-like type 2 receptor β; IREM-2, immune receptor expressed on myeloid cells 2; TREM-2, triggering receptor expressed by myeloid cells 2; and SIRP-β, signal regulatory protein-β. Signals through KARAP/DAP12 antagonize IDO function and DC tolerogenic potential, whereas IFN-γ, through IRF-8/IBCSP, acts in an opposite manner and down-regulated KARAP/DAP12 transcription. IFNG-R indicates interferon-γ receptor.