Mohadeseh Ahmadvand

Canada

MATH-only proteins (MOPs): Emerging immunoregulators in inflammation-related diseases

Mohadeseh Ahmadvand1,2, Azin Tariniya Gilani1, Haroon Nigil2, Ali Abdul-Sater1*

1.School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, Ontario, Canada
2.Schroeder Arthritis Institute, Toronto Western Hospital, Spondylitis Program, University Health Network, Toronto, ON, Canada

Abstract

Background

Inflammation is a vital defensive response of the immune system to pathogens, injury, and tissue damage. However, when prolonged or dysregulated, it can contribute to a range of inflammation-related diseases. A well-balanced and self-limiting inflammatory response is essential for restoring physiological homeostasis. Studying and assessing the presence and levels of immune-related biological markers involved in regulating inflammation plays a pivotal role in treating inflammation-associated conditions.

Methods

In this study, we employed a mixed-methods approach involving both in vitro and in vivo models to investigate inflammatory responses. The in vivo model utilized curdlan-treated SKG mice, while the in vitro models included LPS-stimulated bone marrow-derived macrophages (BMDMs) and human THP-1 cells. These models were used to trigger inflammation-related signalling pathways—particularly TLR-mediated cascades—to evaluate the expression of a novel protein family we designate as MATH-only proteins (MOPs). Real-time quantitative PCR (RT-qPCR) was used to examine MOPs expression and cytokine profiles, including both pro-inflammatory (M1-like; e.g., TNF, IL-1β, IL-6, IFN-b) and anti-inflammatory (M2-like; e.g., IL-10) markers; as well as inflammatory signaling pathways (e.g., NF-kB and ERK1/2) using flow cytometry, and Western blotting.

Results

Our results demonstrate that MOPs are expressed at the mRNA level in immune cells and can be influenced by LPS signalling in both wild-type and transduced THP-1 macrophages. Distinct expression patterns and cytokine profiles were observed between human and murine models, suggesting species- or stimulus-specific regulation. These findings support a potential immunomodulatory function for MOPs and broaden current understanding of MATH domain–mediated signalling beyond TRAF and SPOP proteins. By characterizing these novel proteins, this study addresses a critical gap in inflammation and introduces new molecular candidates for therapeutic exploration.

Conclusions

Our findings reveal differential MOPs expression in response to inflammatory stimuli across both models. These results provide new insights into the regulatory role of MOPs in inflammation induced by microbial exposure, physical stress, and genetic predisposition, contributing to a deeper understanding of how MOPs modulate immune responses.