DAMPs and Inflammasomes: A Clear and Present Danger (jointly sponsored by APS and Physoc)

Symposium — Wednesday, April 25, 2024 — 1:30 PM - 3:00 PM — Convention Center, Room 23
The Physiological Society-UK (PHYSOC) — Chair: Raheela Khan — Co-Chair:

The discovery of inflammasomes at the turn of the century is arguably one of the most significant findings in the field of immunology as attested to by the explosion of,research papers addressing all aspects of inflammasome biology. The basis of inflammasome activation involves coupling between immunological and physiological pathways. The mechanisms whereby typically harmless molecules turn into danger signals is a fascinating area of research, made even more so by the numerous pathophysiologies in which DAMPs and inflammasomes are implicated.

Apart from the classical immune response to microbial infection, inflammatory activation may also be evoked by host-derived ‘danger’ molecules. Termed 'Danger associated molecular patterns’ (DAMPs) or alarmins, these diverse molecules are released in  response to cell or tissue injury, due to perturbed homeostasis, and trigger sterile inflammation. DAMPs are diverse in their structure and chemistry; they include ATP, uric acid, lipids, nucleic acids, even mitochondrial DNA. The resulting sterile inflammation induced by DAMPs  occurs principally via inflammasomes. These large intracellular complexes compartmentalise caspase-1 and interleukin-1b and are thought to mediate exacerbation of inflammatory disorders.The attraction of inflammasomes as therapeutic targets is demonstrated by studies highlighting their role in an emerging catalogue of metabolic, immune, reproductive and neurological disorders. Once assembled, the actual signal(s) whereby the inflammasome is activated has engendered much curiosity; specifically the ‘switch’ that turns on the inflammasome. Quite how such structurally and chemically diverse DAMPs activate the NLRP3 inflammasome is only just being understood and three main mechanisms have been postulated. These are potassium efflux through the purinergic P2X7 receptor, generation of reactive oxygen species and lysosomal destabilisation. The main aims of this symposium are 1) to provide a detailed insight into the diversity of DAMPs and 2) the physiological mechanisms (specifically the P2X7 receptor), deployed for inflammasome activation and resolution of inflammation through targeting of the inflammasome complex.

Speakers

• Unconventional roles for gasdermin D in pyroptosis-independent IL-1b release from neutrophils during inflammasome signalling
  Eric Pearlman — Univ. of California-Irvine


• Inflammasomes beyond IL-1 and cell death.
  Vijay Rathinam — Uonn Hlth. Sch. of Med., Farmington


• Alpaca nanobodies reveal mechanistic details of DAMP-induced inflammasome signaling.
  Florian Schmidt — Univ. of Bonn