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TRIM21 interacts with IκBα and negatively regulates NF-κB activation in Corynebacterium pseudotuberculosis-infected

Chanyu Wu1, Xiaohan Wang1, Xincan Li1

  • 1College of Veterinary Medicine, Southwest University, No. 160 Xueyuan Road, Rongchang District, Chongqing 402460, China.

Veterinary Immunology and Immunopathology
|February 28, 2025
PubMed

Insights

Tripartite motif-containing protein 21 (TRIM21) controls inflammation during Corynebacterium pseudotuberculosis infection. TRIM21 stabilizes IκBα, reducing its phosphorylation and inhibiting the NF-κB pathway, offering a potential therapeutic target.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Corynebacterium pseudotuberculosis causes chronic inflammation and abscesses.
  • Tripartite motif-containing protein 21 (TRIM21) is known to regulate inflammatory responses.
  • The precise mechanism by which TRIM21 modulates C. pseudotuberculosis-induced inflammation is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism by which TRIM21 regulates pro-inflammatory cytokine production during C. pseudotuberculosis infection.
  • To investigate the interaction between TRIM21 and key components of the NF-κB signaling pathway.

Main Methods:

  • Macrophage infection models with C. pseudotuberculosis.
  • Western blotting to detect protein phosphorylation (IκB and p65).
  • Co-immunoprecipitation to assess protein-protein interactions (TRIM21 and IκBα).
  • Ubiquitination assays to determine linkage types (K48 vs. K63).

Main Results:

  • C. pseudotuberculosis infection induced phosphorylation of IκB and p65 in macrophages.
  • TRIM21 directly interacted with IκBα via its PRY/SPRY domain.
  • TRIM21 binding stabilized IκBα, leading to decreased IκBα phosphorylation.
  • TRIM21 promoted K48-linked ubiquitination of IκBα, distinct from K63 linkage.
  • TRIM21 was confirmed to negatively regulate the canonical NF-κB pathway.

Conclusions:

  • TRIM21 inhibits canonical NF-κB activation during C. pseudotuberculosis infection by stabilizing IκBα and reducing its phosphorylation.
  • TRIM21's role in regulating IκBα ubiquitination provides a novel insight into its anti-inflammatory function.
  • Targeting the TRIM21-IκBα interaction presents a potential therapeutic strategy for controlling C. pseudotuberculosis-induced inflammation.
Keywords:
Corynebacterium pseudotuberculosisMacrophagesNF-κBTRIM21

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