Figure 6

Model demonstrating how LAIR-1 contributes to immune tolerance. (A) In the resting state, Csk constitutively associates with LAIR-1. (B) When LAIR-1 is engaged in the presence of C1q, Hck phosphorylates the ITIMs on LAIR-1. Phosphorylated LAIR-1 recruits SHP-1 and induces the phosphatase activity of SHP-1. SHP-1 mediates the inhibition of monocytes by dephosphorylating the activating tyrosine residues of various intracellular tyrosine-phosphorylation substrates and by inhibiting nuclear translocation of IRFs or NF-κB resulting in cytokine production.