Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2019 Aug 21

PMID 31426355

Citations 11

Authors

Manjusri Das

Moonmoon Deb

Dipranjan Laha

Matthew Joseph

Suman Kanji

Reeva Aggarwal

O Hans Iwenofu

Vincent J Pompili

Wael Jarjour

Hiranmoy Das

Affiliations

Soon will be listed here.

Abstract

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic differentiation, matrix metalloproteinases (MMPs), and inflammatory cytokines in K/BxN serum-induced mice. The severities of RA pathogenesis, as well as the causative and resultant cellular and molecular factors, were further confirmed in monocyte-specific KLF2 deficient mice. In addition, induction of RA resulted in a decreased level of KLF2 in monocytes isolated from both mice and humans along with higher migration of activated monocytes to the RA sites in humans. Mechanistically, overexpression of KLF2 decreased the level of MMP9; conversely, knockdown of KLF2 increased MMP9 in monocytes along with enrichment of active histone marks and histone acetyltransferases on the MMP9 promoter region. These findings define the critical regulatory role of myeloid KLF2 in RA pathogenesis.

Citing Articles

Krüppel-like factors family in health and disease.

Xiang T, Yang C, Deng Z, Sun D, Luo F, Chen Y MedComm (2020). 2024; 5(9):e723.

PMID: 39263604 PMC: 11387732. DOI: 10.1002/mco2.723.

KLF transcription factors in bone diseases.

Wang H, Han J, Dmitrii G, Ning K, Zhang X J Cell Mol Med. 2024; 28(8):e18278.

PMID: 38546623 PMC: 10977429. DOI: 10.1111/jcmm.18278.

Krüppel-like factor 2 (KLF2), a potential target for neuroregeneration.

Hansda S, Prateeksha P, Das H Neural Regen Res. 2024; 19(11):2327-2328.

PMID: 38526258 PMC: 11090422. DOI: 10.4103/NRR.NRR-D-23-01758.

Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.

Niu Q, Gao J, Wang L, Liu J, Zhang L Front Immunol. 2022; 13:1034050.

PMID: 36466887 PMC: 9716075. DOI: 10.3389/fimmu.2022.1034050.

Heterozygous premature termination in zinc-finger domain of Krüppel-like factor 2 gene associates with dysregulated immunity.

Pernaa N, Keskitalo S, Chowdhury I, Nissinen A, Glumoff V, Keski-Filppula R Front Immunol. 2022; 13:819929.

PMID: 36466816 PMC: 9716311. DOI: 10.3389/fimmu.2022.819929.

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