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TRIM63 and Atrogin-1 are key drivers of systemic and muscle inflammation in patients with idiopathic inflammatory myopathies

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11

 

  1. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  2. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  3. Red de Apoyo a la Investigación, Coordinación de Investigación Científica, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  4. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  5. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  6. Microsopy Unit, Instituto de Investigación Biomédica Básica, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  7. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  8. Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  9. Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  10. Red de Apoyo a la Investigación, Coordinación de Investigación Científica, Universidad Nacional Autónoma de México, Mexico City, Mexico.
  11. Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. diana.gomezm@incmnsz.mx

CER18153
2025 Vol.43, N°2
PI 0326, PF 0333
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PMID: 39946176 [PubMed]

Received: 09/09/2024
Accepted : 10/02/2025
In Press: 12/02/2025
Published: 26/02/2025

Abstract

OBJECTIVES:
The ubiquitin proteasome system is the main mediator of inflammation-induced muscle atrophy through the expression of TRIM63 and Atrogin-1. The aim of this study was to address the expression of these ubiquitin ligases and their relationship with inflammatory and atrophy parameters of patients with idiopathic inflammatory myopathies (IIM).
METHODS:
We recruited 37 adult IIM patients, and 10 age and sex-matched healthy donors. We assessed the proportion of different peripheral blood mononuclear cells (PBMC) subsets expressing TRIM63 and Atrogin-1 and the serum amount of theses ubiquitin ligases, cytokines, and chemokines, using multiparametric flow-cytometry, ELISA and luminometry respectively. The muscle expression of TRIM63 and Atrogin-1 was assessed by confocal microscopy. We compared the quantitative variables with the Mann-Whitney U test and assessed the correlations with Spearman Rho.
RESULTS:
IIM patients had a higher proportion of TRIM63+ CD4+ T cells (24.56 (7.71-53.23) vs. 2.55 (0.42-4.51), p<0.0001), TRIM63+ CD8+ T cells (15.1 (3.22-37.40) vs. 1.06 (0.83-2.45), p=0.0002), TRIM63+ monocytes (14.09 (3.25-29.80) vs. 1.97 (0.59-7.64), p=0.011), Atrogin-1+ CD4+ T cells (27.30 (6.61-64.19) vs. 2.55 (0.42-4.51), p<0.0001), Atrogin-1+ CD8+ T cells (14.88 (5.99-34.30) vs. 2.33 (0.60-8.01), p=0.001), and Atrogin1+ monocytes (17.38 (8.93-47.37) vs. 1.41 (0.79-3.77), p<0.0001). Muscle from IIM patients had a higher expression of TRIM63 and Atrogin-1. TRIM63+ CD8+ T cells mainly correlated with serum IL-2, IL-4, IL-8, IL-10, G-CSF, and TNF-a.
CONCLUSIONS:
TRIM63 and Atrogin-1 are expressed in PBMC and muscle from patients with IIM and correlate with serum cytokines, and chemokines. This mechanism may contribute to the inflammation-induced muscle atrophy in IIM.

DOI: https://doi.org/10.55563/clinexprheumatol/p2lma6

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