Harnessing the therapeutic potential of TIMP-1 in autoimmune inflammation: A prospective insight

Shangomitra Bhattacharjee1, Mahaboobkhan Rasool1

  • 1Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.

PubMed

Tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) have recently attracted significant attention owing to their newly discovered cytokine function. These findings prompted a reevaluation of TIMP-1's role as an inhibitor of matrix metalloproteinase. Elevated TIMP-1 levels have been observed in various autoimmune conditions, influencing disease outcomes in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Furthermore, TIMP-1 affects context-dependent metabolic profiles, enhances glycolytic turnover in monocytes, and is associated with ferroptosis in patients with rheumatoid arthritis. TIMP-1 also supports MHC-I expression and CD8 + T-cell activation, indicating a more active role in autoimmune conditions. Considering the expanding body of knowledge regarding TIMP-1 and its significant role in modifying metabolic profiles and disease outcomes, we carefully reviewed the contrasting functions of TIMP-1. Additionally, we summarize the upstream activators and signaling pathways involved in TIMP-1 activation and its reciprocal effects. Although TIMP-1 expression is linked to diverse disease outcomes, it is advisable to adopt a more nuanced approach to utilizing TIMP-1 depending on the specific disease context. This review proposes various strategies for targeting TIMP-1 as a therapeutic intervention to modulate the outcomes of autoimmune disorders.

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