The role of mast cells in autoinflammation.

ABSTRACT

The concept of autoinflammation was proposed to define a new class of immune disorders categorized by self-directed inflammation that is driven via activation of innate immune pathways. Within innate immunity, inflammasomes serve as intracellular signaling platforms to endogenous danger molecules and pathogens. Their key function is the cleavage of pro-interleukin-1ß (pro-IL-1ß) into its active form to promote inflammation and programmed cell death. A growing number of inflammasome sensors were described, among which NLR family pyrin domain containing 3 (NLRP3) is the best-studied sensor. Besides macrophages, monocytes, and other innate immune cells, mast cells (MCs) were shown to express functional inflammasomes too. Also, MCs are both, a source and target of IL-1ß. Here we review the functional relevance and role of MC inflammasomes and MC-derived IL-1ß in contributing to the inflammation at the skin, joints, and central nervous system in rare monogenic autoinflammatory conditions and also common inflammatory and degenerative diseases.