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Review
. 2024 May:262:110168.
doi: 10.1016/j.clim.2024.110168. Epub 2024 Mar 7.

A Disintegrin and metalloproteinase carves T cell abnormalities and pathogenesis in systemic lupus erythematosus

Masataka Umeda  1 , Abhigyan Satyam  2 , Nobuya Yoshida  2 , Atsushi Kawakami  3
Affiliations
Review

A Disintegrin and metalloproteinase carves T cell abnormalities and pathogenesis in systemic lupus erythematosus

Masataka Umeda et al. Clin Immunol. 2024 May.

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder impacting various organs, notably prevalent in women of reproductive age. This review explores the involvement of a disintegrin and metalloproteinases (ADAMs) in SLE pathogenesis. Despite advancements in understanding SLE through genome and transcriptome studies, the role of ADAMs in post-translational regulations remains insufficiently explored. ADAMs, transmembrane proteins with diverse functions, impact cell adhesion, migration, and inflammation by shedding cell surface proteins, growth factors, and receptors. Notably, ADAM9 is implicated in Th17 cell differentiation, which is crucial in SLE pathology. ADAM10 and ADAM17 play pivotal roles in T-cell biology, influencing immune cell development and differentiation. Elevated soluble ADAM substrates in SLE patients serve as potential biomarkers correlating with disease activity. Targeting ADAMs or their substrates offers promising therapeutic avenues for SLE management and treatment enhancement.

Keywords: A Disintegrin and metalloproteinase; ADAM9; Systemic lupus erythematosus; T cells.

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Conflict of interest statement

Disclosure statement

The authors have no conflicts of interest or other disclosures to describe.

Figures

Fig. 1.
Fig. 1.. Structure and functions of ADAMs.
Fig. 2.
Fig. 2.. The Impact of ADAMs in patients with SLE
A) ADAM10 and ADAM17 disrupt the Gas6/Axl-mediated inhibitory pathway to NFκB by cleaving Axl on the surface of PBMCs and macrophages. B) ADAM10 cleaves the transmembrane activator and CAML interactor (TACI) on the surface of B cells, converting it to soluble TACI. Elevated levels of soluble TACI in sera from SLE patients positively correlate with disease activity. C) ADAM10 and ADAM17 cleave and solubilize cell surface fractalkine. The released soluble fractalkine induces cell migration activity against natural killer (NK) cells, T cells, and monocytes. D) ADAM10 and ADAM17 cleave and solubilize Tim-3, a marker of T cell surface exhaustion. Increased levels of soluble Tim-3 in the sera of SLE patients positively correlate with disease activity. E) ADAM9 executes the cleavage of the latency-associated peptide (LAP) of latent bioactive transforming growth factor (TGF)-β1, generating bioactive TGF-β1 that facilitates SMAD2/3 phosphorylation and activation.
See this image and copyright information in PMC

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