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

Nat Commun. 2014;5:3146. doi: 10.1038/ncomms4146.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Apoptosis*
  • Autoimmunity*
  • Class Ia Phosphatidylinositol 3-Kinase / metabolism*
  • Mice
  • Phagocytosis
  • Receptors, Immunologic / metabolism*

Substances

  • CLM-1 protein, mouse
  • Receptors, Immunologic
  • Class Ia Phosphatidylinositol 3-Kinase