Interferon-stimulated GTPases in autoimmune and inflammatory diseases: promising role for the guanylate-binding protein (GBP) family

Abstract

Human IFNs are secreted cytokines shown to stimulate the expression of over one thousand genes. These IFN-inducible genes primarily encode four major protein families, known as IFN-stimulated GTPases (ISGs), namely myxovirus-resistance proteins, guanylate-binding proteins (GBPs), p47 immunity-related GTPases and very large inducible guanosine triphosphate hydrolases (GTPases). These families respond specifically to type I or II IFNs and are well reported in coordinating immunity against some well known as well as newly discovered viral, bacterial and parasitic infections. A growing body of evidence highlights the potential contributory and regulatory roles of ISGs in dysregulated inflammation and autoimmune diseases. Our focus was to draw attention to studies that demonstrate increased expression of ISGs in the serum and affected tissues of patients with RA, SS, lupus, IBD and psoriasis. In this review, we analysed emerging literature describing the potential roles of ISGs, particularly the GBP family, in the context of autoimmunity. We also highlighted the promise and implications for therapeutically targeting IFNs and GBPs in the treatment of rheumatic diseases.

Regulation of Synovial Inflammation and Tissue Destruction by Guanylate Binding Protein 5 in Synovial Fibroblasts From Patients With Rheumatoid Arthritis and Rats With Adjuvant‐Induced Arthritis

“…Though we characterized the role of GBP-5 in the context of inflammation and tissue destruction (GBPs reviewed in ref. 12), the study has several limitations that could potentially lead to future investigation. First, further mechanistic studies are needed to identify which pathways are used by IL-1β to induce GBP-5 expression, given that IFNGRII knockdown did not inhibit IL-1β-induced GBP-5 expression in RASFs.…”

“…The GBP family comprises 7 members (GBP1-GBP7) that are expressed in human cells and are highly responsive to IFN stimulation (8). Besides their function in immunity (9), studies suggest that they regulate cellular proliferation, angiogenesis, and tissue invasion (10)(11)(12). Among the GBP family members, GBP-5 has recently been shown to play a crucial role in immunity against infections through NLRP3 inflammasome activation in macrophages (13)(14)(15).…”

Domain motions, dimerization, and membrane interactions of the murine guanylate binding protein 2

“…The superfamily of dynamin-like proteins includes the 65-73 kDa guanylate binding proteins (GBPs) that are involved in various structural changes for remodeling cellular membranes or causing fusion/fission events via guanosine-5'-triphosphate (GTP) binding and hydrolysis [1][2][3][4] . GBPs are induced by interferon-γ and they accumulate at membranes of intracellular pathogens and bacteria to initiate host cell survival responses [5][6][7][8][9] , including in autoimmune and inflammatory diseases 4,10,11 .…”

Zebrafish intestinal transcriptome highlights subdued inflammatory responses to dietary soya bean and efficacy of yeast β‐glucan

“…The upregulation of ifi30 in the PM group may partly be explained by the recognition and processing of β‐glucan by antigen‐presenting cells in the intestine. Although the expression of vlig‐1 is induced by interferons, the functional significance of its downregulation is yet to be revealed (Haque et al., 2021). The gene ccdc134 serves as an immune cytokine promoting CD8(+) T‐cell activation (Huang et al., 2014), and hence, the downregulated expression of ccdc134 in the PM group suggests an immunomodulatory response following β‐glucan feeding.…”