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An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
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An Adoptive Transfer Model of Rheumatoid Arthritis in Mice

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METTL14-Mediated m6A Modification of TNFAIP3 Involved in Inflammation in Patients With Active Rheumatoid Arthritis

Jifeng Tang1, Ziqing Yu2, Jinfang Xia3

  • 1Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China and Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Arthritis & Rheumatology (Hoboken, N.J.)
|June 16, 2023
PubMed
Abstract

Insights

N6-methyladenosine (m6A) levels and the m6A writer METTL14 are decreased in rheumatoid arthritis (RA) patients. Targeting m6A modification may offer new treatment strategies for RA management.

Area of Science:

  • Immunology
  • Epigenetics
  • Molecular Biology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
  • N6-methyladenosine (m6A) is the most prevalent internal mRNA modification, playing crucial roles in various biological processes.
  • The role of m6A modification in RA pathogenesis remains incompletely understood.

Purpose of the Study:

  • To investigate the role of m6A modification in the progression of rheumatoid arthritis (RA).
  • To explore the function of methyltransferase-like 14 (METTL14) in RA-associated inflammation.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) from RA patients and healthy controls were analyzed for m6A levels and related proteins using PCR, Western blot, and ELISA.
  • Methyltransferase-like 14 (METTL14) function was assessed using MeRIP sequencing and RNA immunoprecipitation assays.
  • Collagen antibody-induced arthritis (CAIA) mouse models were employed for in vivo studies.

Main Results:

  • m6A levels and METTL14 expression were reduced in PBMCs of active RA patients, correlating negatively with disease activity (DAS28).
  • METTL14 knockdown exacerbated RA inflammation by increasing IL-6 and IL-17 secretion in PBMCs and in CAIA mice.
  • m6A modification was found to regulate the expression of TNFAIP3, a key suppressor of the NF-κB pathway, by affecting mRNA stability and translocation.

Conclusions:

  • m6A modification plays a critical role in regulating inflammation during RA progression.
  • METTL14 is a key regulator of RA-associated inflammation.
  • Targeting m6A modification presents a potential novel therapeutic strategy for managing RA.

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