Targeting CD44 in mast cell regulation.

IMPORTANCE OF THE FIELD: Accumulating evidence suggests that mast cells are involved in a wide variety of immune responses including chronic inflammation, immune tolerance and tumor immunity. Mast cells originate from hematopoietic stem cells and undergo terminal differentiation in the tissues, in which they are ultimately resident. Heterogeneity of tissue mast cells is, therefore, one of the key concepts for a better understanding of various immune responses. AREAS COVERED IN THIS REVIEW: This review describes the candidate genes involved in regulation of cutaneous mast cell differentiation, with a particular attention to CD44, which is the primary receptor for hyaluronan. WHAT THE READER WILL GAIN: CD44 is involved in various aspects of cutaneous inflammation. Regarding mast cells, CD44 is upregulated upon differentiation and maturation of mast cells, and plays a critical role in regulation of cutaneous mast cell number. Since both degradation and decrease of hyaluronan are often observed upon chronic inflammation, CD44 might be involved in modulation of local immune responses through regulation of cutaneous mast cell functions. TAKE HOME MESSAGE: Understanding of cutaneous immune responses should require clarification of local mast cell functions, a part of which is regulated by extracellular matrix components and their membrane receptors.