Mechanistic insight on the role of iRhom2-TNF-α-BAFF signaling pathway in various autoimmune disorders

Shradha Devi Dwivedi; Rashi Shukla; Krishna Yadav; Lokendra Singh Rathor; Deependra Singh; Manju Rawat Singh

doi:10.1016/j.jbior.2023.101011

Mechanistic insight on the role of iRhom2-TNF-α-BAFF signaling pathway in various autoimmune disorders

Adv Biol Regul. 2023 Dec 14:92:101011. doi: 10.1016/j.jbior.2023.101011. Online ahead of print.

Authors

Shradha Devi Dwivedi¹, Rashi Shukla¹, Krishna Yadav², Lokendra Singh Rathor¹, Deependra Singh¹, Manju Rawat Singh³

Affiliations

¹ University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G), 492010, India.
² Raipur Institute of Pharmaceutical Educations and Research, Sarona, Raipur, Chhattisgarh, 492010, India.
³ University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G), 492010, India. Electronic address: manjursu@gmail.com.

PMID: 38151421
DOI: 10.1016/j.jbior.2023.101011

Abstract

iRhom2 is a crucial cofactor involved in upregulation of TNF receptors (TNFRs) and the pro-inflammatory cytokine tumor necrosis factor (TNF-) from the cell surface by ADAM17. Tumor necrosis factor- α converting enzyme (TACE) is another name given to ADAM17. Many membrane attached biologically active molecules are cleaved by this enzyme which includes TNFRs and the pro-inflammatory cytokine tumor necrosis factor- α. The TNF receptors are of two types TNFR1 and TNFR2. iRhom2 belongs to the pseudo-protease class of rhomboid family, its abundance is observed in the immune cells. Biological activity of ADAM17 is affected in multiple levels by the iRhom2. ADAM17 is trafficked into the Golgi apparatus by the action of iRhom2, where it gets matured proteolytically and is stimulated to perform its function on the cell surface. This process of activation of ADAM17 results in the protection of the organism from the cascade of inflammatory reactions, as this activation blocks the TNF- α mediated secretion responsible for inflammatory responses produced. Present paper illustrates about the iRhom2-TNF-α-BAFF signaling pathway and its correlation with several autoimmune disorders such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, Hemophilia Arthropathy, Alzheimer's disease and Tylosis with esophageal cancer etc.

Keywords: Autoimmune diseases; BAFF signaling; TNF-α; iRhom1 and iRhom2 receptors; iRhom2.

Publication types

Review