Novel collectin/C1q receptor mediates mast cell activation and innate immunity

Abstract

Mast cells play a critical role in innate immunity, allergy, and autoimmune diseases. The receptor/ligand interactions that mediate mast cell activation are poorly defined. The α₂β₁ integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1 (MMP-1), endorepellin, and several viruses, has been implicated in normal developmental, inflammatory, and oncogenic processes. We recently reported that α₂ integrin subunit–deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes–and zymosan-induced peritonitis. Peritoneal mast cells require α₂β₁ integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the α₂β₁ integrin induces activation and cytokine secretion remain unknown. We now report that the α₂β₁ integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the α₂β₁ integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the α₂β₁ integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.