Protective Role of the MER Tyrosine Kinase Efferocytosis in Rheumatoid Arthritis Models

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2018 May 1

PMID 29706963

Citations 33

Authors

Claire E J Waterborg

Silke Beermann

Mathijs G A Broeren

Miranda B Bennink

Marije I Koenders

Peter L E M van Lent

Wim B van den Berg

Peter M van der Kraan

Fons A J van de Loo

Affiliations

Soon will be listed here.

Abstract

Objective: Rheumatoid arthritis (RA) is a chronic and progressive joint disease. It appears that anti-inflammatory feedback mechanisms that could restrain joint inflammation and restore homeostasis are insufficient to perform this control. In this study, we investigated the contribution of the MER tyrosine kinase-mediated anti-inflammatory response on arthritis and whether targeting MER could be a valid approach to treat RA.

Methods: KRN serum transfer arthritis (KRN STA) was induced in either -deficient mice or in mice that adenovirally overexpressed . Human synovial micromasses were treated with MER-specific antibodies or PROS1. Collagen-induced arthritis (CIA) mice were treated with MER-specific agonistic antibodies or by viral overexpression of .

Results: mice showed exacerbated arthritis pathology, whereas overexpression diminished joint pathology in KRN STA. Human synovial micromasses challenged with MER-specific antibodies enhanced the secretion of inflammatory cytokines, whereas stimulating MER with PROS1 reduced the secretion of these cytokines, confirming the protective role of MER. Next, we treated CIA mice with MER-specific agonistic antibodies, and this unexpectedly resulted in exacerbated arthritis pathology. This was associated with increased numbers of apoptotic cells in their knee joints and higher serum levels of interleukin (IL)-16C, a cytokine released by secondary necrotic neutrophils. Apoptotic cell numbers and IL-16C levels were enhanced during arthritis in mice and reduced in -overexpressing mice.

Conclusion: MER plays a protective role during joint inflammation and activating MER by its ligand PROS1 ameliorates disease. Treatment of mice with MER receptor agonistic antibodies is deleterious due to its counterproductive effect of blocking efferocytosis in the arthritic joint.

Citing Articles

Efferocytosis and inflammation: a bibliometric and systematic analysis.

Cao X, Li F, Xie X, Ling G, Tang X, He W Front Med (Lausanne). 2025; 12:1498503.

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IĸBζ as a Central Modulator of Inflammatory Arthritis Pathogenesis.

Swarnkar G, Naaz M, Mims D, Gupta P, Peterson T, Christopher M Arthritis Rheumatol. 2024; 77(2):124-139.

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Transcriptional analysis of efferocytosis in mouse skin wounds.

Krause W, King D, Horsley V bioRxiv. 2024; .

PMID: 39185146 PMC: 11343138. DOI: 10.1101/2024.08.12.607219.

Efferocytosis and Bone Dynamics.

Batoon L, Hawse J, McCauley L, Weivoda M, Roca H Curr Osteoporos Rep. 2024; 22(5):471-482.

PMID: 38914730 DOI: 10.1007/s11914-024-00878-y.

Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms.

Sheng Y, Hu W, Chen S, Zhu X Front Immunol. 2024; 15:1275203.

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