Identification and characterization of the mechanisms and relevance of inflammasome activation in mast cells

• Applicant: Professor Dr. Marcus Maurer (†)
• Subject Area: Dermatology ; Immunology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255956848

• Final Report Year: 2018

Final Report Abstract

1) Mast cells express functional inflammasomes. 2) Mast cells require high concentrations of LPS for TLR4 stimulation and subsequent NF-κB activation, because they do not express CD14. In vivo, LPS concentrations in the vicinity of MCs are not high enough for TLR4 activation and subsequent inflammasome assembly in MCs in wild type mice upon bacterial infection. 3) When pretreated with high LPS doses, UV-B light causes murine mast cells to release IL-1β in vitro. This is either mediated by activation of the inflammasome or, which seems more likely, by an alternative pathway or secondary effects. 4) In mice, neutrophil attraction and infiltration after UV-B exposure does not seem to be mediated by the inflammasome, as we observed almost no differences between wt and inflammasome-deficient mice. 5) In disease driven by an overreactive inflammasome (Schnitzler’s syndrome, CAPS), mast cells largely contribute to the disease activity via release of IL-1β and IL-6. Neutrophilic infiltrates in these diseases also largely contribute to disease activity by secretion of inflammasome-derived IL-1β and IL-18.

Publications

• (2017) “Use of skin biomarker profiles to distinguish Schnitzler syndrome from chronic spontaneous urticaria: results of a pilot study” Br J Dermatol 178(2):561-562
  Bonnekoh H, Scheffel J, Maurer M, Krause K
  
• (2018) “The role of mast cells in autoinflammation” Immunol Rev 282:265-275
  Bonnekoh H, Scheffel J, Kambe N, Krause K