Unraveling the role of NLRP3 inflammasome in allergic inflammation: implications for novel therapies

Front Immunol. 2024 Jul 26:15:1435892. doi: 10.3389/fimmu.2024.1435892. eCollection 2024.

Abstract

Allergic diseases like asthma, allergic rhinitis and dermatitis pose a significant global health burden, driving the search for novel therapies. The NLRP3 inflammasome, a key component of the innate immune system, is implicated in various inflammatory diseases. Upon exposure to allergens, NLRP3 undergoes a two-step activation process (priming and assembly) to form active inflammasomes. These inflammasomes trigger caspase-1 activation, leading to the cleavage of pro-inflammatory cytokines (IL-1β and IL-18) and GSDMD. This process induces pyroptosis and amplifies inflammation. Recent studies in humans and mice strongly suggest a link between the NLRP3 inflammasome, IL-1β, and IL-18, and the development of allergic diseases. However, further research is needed to fully understand NLRP3's specific mechanisms in allergies. This review aims to summarize the latest advances in NLRP3 activation and regulation. We will discuss small molecule drugs and natural products targeting NLRP3 as potential therapeutic strategies for allergic diseases.

Keywords: IL-1β/IL-18 signaling; NLRP3 inflammasome; allergic diseases; pyroptosis; therapeutic potential.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Hypersensitivity* / drug therapy
  • Hypersensitivity* / immunology
  • Hypersensitivity* / metabolism
  • Hypersensitivity* / therapy
  • Inflammasomes* / immunology
  • Inflammasomes* / metabolism
  • Inflammation* / immunology
  • Inflammation* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes
  • NLRP3 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants Natural Science Foundation of China (No.822047435 and 81773978), Guangdong Basic and Applied Basic Research Foundation (2023A1515012207 and 2022A1515111103), Shenzhen Innovation of Science and Technology Commission (No. JCYJ20200109144625016 and JCYJ20220531091602005), Longgang District Science and Technology Plan (No. LGKCYLWS2022010, LGKCYLWS2022031, LGKCYLWS2022003 and LWGJ2023-089), and Shenzhen Key Medical Discipline Construction Fund (No. SZXK039). Longgang Medical Discipline Construction Fund (Key Medical Discipline in Longgang District).