[HTML][HTML] p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression

L Tian, SC Choi, Y Murakami, J Allen… - Nature …, 2014 - nature.com
L Tian, SC Choi, Y Murakami, J Allen, HC Morse III, CF Qi, K Krzewski, JE Coligan
Nature communications, 2014nature.com
Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that
mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and
regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact
sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals
that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary
for enhanced CD300f-mediated phagocytosis through the recruitment of the p85α regulatory …
Abstract
Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K). CD300f-PI3K association leads to activation of downstream Rac/Cdc42 GTPase and mediates changes of F-actin that drive AC engulfment. Importantly, primary macrophages from CD300f-deficient mice have impaired phagocytosis of ACs. The biological consequence of CD300f deficiency is predisposition to autoimmune disease development, as FcγRIIB-deficient mice develop a systemic lupus erythematosus-like disease at a markedly accelerated rate if CD300f is absent. In this report we identify the mechanism and role of CD300f in AC phagocytosis and maintenance of immune homeostasis.
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