Inflammasome Activation in Radiation-Induced Inflammatory Responses

Exposure to ionising radiation triggers a complex inflammatory cascade in which cytosolic multiprotein platforms, known as inflammasomes, play a central role. Sensor proteins such as NLRP3 and AIM2 detect radiation-induced cellular stress and DNA damage, assembling with the adaptor protein ASC to recruit and activate caspase-1. Active caspase-1 cleaves pro-IL-1β and pro-IL-18 into their mature, secreted forms and processes gasdermin D to its pore-forming fragment, thereby initiating pyroptotic cell death. The release of interleukins, danger-associated molecular patterns and membrane vesicles amplifies local tissue injury, recruits immune cells and can precipitate non-resolving inflammation and fibrotic remodelling. While inflammasome activation contributes to tumour control by enhancing antigen presentation and immune surveillance, excessive or prolonged signalling underlies radiation-induced complications in lung, intestine, cardiovascular and haematopoietic tissues. Therapeutic modulation of key inflammasome components thus holds promise both to potentiate radiotherapy efficacy against neoplastic cells and to limit collateral damage to normal organs.

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Inflammasome Activation in Radiation-Induced Inflammatory Responses publication trend

The graph below shows the total number of articles in inflammasome activation in radiation-induced inflammatory responses across all publications each year (not limited to Nature Index journals).

Technical terms

Inflammasome: A cytosolic multiprotein complex that senses stress or pathogen signals and activates inflammatory caspases.

NLRP3: A nucleotide-binding oligomerisation domain receptor that recognises diverse danger signals and initiates inflammasome assembly.

AIM2: An absent in melanoma 2 protein that detects cytosolic double-stranded DNA and triggers inflammasome formation.

Caspase-1: A protease activated by inflammasomes that processes pro-interleukins and cleaves gasdermin D.

Gasdermin D: An effector protein whose N-terminal fragment forms membrane pores leading to pyroptotic cell lysis.

Pyroptosis: A lytic form of programmed cell death associated with inflammatory cytokine release and membrane rupture.

References

1. Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy. Cell Death Discovery (2024).
2. Radiation causes tissue damage by dysregulating inflammasome–gasdermin D signaling in both host and transplanted cells. PLOS Biology (2020).
3. Hunting down NLRP3 inflammasome: An executioner of radiation-induced injury. Frontiers in Immunology (2022).