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Inflammasome activation and Th17 responses.

Jian Deng1, Xiao-Qiang Yu2, Pei-Hui Wang3

  • 1School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.

Molecular Immunology
|February 12, 2019
PubMed
Summary
This summary is machine-generated.

Immune sensing activates innate immunity, with inflammasomes producing IL-1β and IL-18. These cytokines drive adaptive immunity, particularly Th17 cells, offering therapeutic targets for inflammatory diseases and cancers.

Keywords:
IL-17IL-1RIL-1βInflammasomesT-helper cellsTh17

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Area of Science:

  • Immunology
  • Molecular Biology
  • Inflammation Research

Background:

  • Immune sensing of exogenous and endogenous danger signals activates innate immunity and primes adaptive immunity.
  • While transcriptional responses are well-studied, the impact of post-translational modifications on adaptive immunity remains less explored.
  • Inflammasomes are key sensors activated by diverse stimuli, leading to the maturation of crucial inflammatory cytokines.

Purpose of the Study:

  • To investigate the role of inflammasome-mediated post-translational responses in modulating adaptive immunity.
  • To elucidate the signaling pathways downstream of inflammasome activation, focusing on IL-1β and IL-18.
  • To explore the therapeutic potential of targeting inflammasomes and IL-1/IL-1R signaling in Th17-associated pathologies.

Main Methods:

  • Activation of inflammasomes by various exogenous and endogenous molecular patterns.
  • Analysis of pro-caspase-1 cleavage and subsequent maturation of IL-1β and IL-18.
  • Assessment of cytokine-induced immune cell activation, including phagocytes and T helper cells.
  • Investigation of IL-1β synergy with IL-6 and IL-23 in driving Th17 cell differentiation.

Main Results:

  • Inflammasome activation leads to the autocatalytic cleavage of pro-caspase-1, generating bioactive IL-1β and IL-18.
  • IL-1β and IL-18 promote host defense by activating phagocytes and inducing Th17 and Th1 adaptive immune responses.
  • IL-1β, in conjunction with IL-6 and IL-23, is critical for the differentiation of IL-17-producing Th17 cells.

Conclusions:

  • Post-translational regulation by inflammasomes significantly shapes adaptive immunity, particularly Th17 responses.
  • Targeting inflammasomes and the IL-1/IL-1R pathway presents a promising strategy for treating Th17-associated inflammatory diseases and cancers.
  • This research offers novel insights for drug development in autoimmune disorders and oncology.