Human leukocyte antigen c (HLA‐C) is a polymorphic membrane protein encoded by the HLA‐C gene in the class I major histocompatibility complex. HLA‐C plays an essential role in protection against cancer and viruses but has also been implicated in allograft rejection, preeclampsia, and autoimmune disease. This review summarizes reports and proposed mechanisms for the accessory role of HLA‐C in rheumatic diseases. Historically, contributions of HLA‐C to rheumatic diseases were eclipsed by the stronger association with HLA‐DRB1 alleles containing the “shared epitope” with rheumatoid arthritis. Larger genetic association studies and more powerful analytical approaches have revealed independent associations of HLA‐C with rheumatic disease–associated phenotypes, including development of anticitrullinated peptide antibodies. HLA‐C functions by presenting antigens to T cells and by binding activatory and inhibitory receptors on natural killer (NK) cells, but the exact mechanisms by which the HLA‐C locus contributes to autoimmunity are largely undefined. Studies have suggested that HLA‐C and NK cell receptor polymorphisms may predict responsiveness to pharmacotherapy. Understanding the mechanisms of the role of HLA‐C in rheumatic disease could uncover therapeutic targets or guide precision pharmacologic treatments.

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.

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TGF β-activated kinase 1 (TAK1) is an important participant in inflammatory pathogenesis for diseases such as rheumatoid arthritis (RA) and gouty arthritis. The central position it occupies between the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways makes it an attractive therapeutic target. As this field has developed in recent years, several novel inhibitors have been presented as having specific activity that reduces the TAK1 function either covalently as in the case of 5Z-7-oxozeanol (5Z7O) or reversibly (NG-25). However, the mechanism through which takinib elicits its anti-inflammatory activity remains elusive. While this inhibitor shows great promise, a thorough analysis of its inhibitor function and its potential off-target effects is necessary before addressing its clinical potential or its use in inflammatory conditions. An analysis through Western blot showed an unexpected increase in IL-1β-induced TAK1 phosphorylation—a prerequisite for and indicator of its functional potential—by takinib while simultaneously demonstrating the inhibition of the JAK/STAT pathway in human rheumatoid arthritis synovial fibroblasts (RASFs) in vitro. In THP-1 monocyte-derived macrophages, takinib again led to the lipopolysaccharide-induced phosphorylation of TAK1 without a marked inhibition of the TAK1 downstream effectors, namely, of c-Jun N-terminal kinase (JNK), phospho-c-Jun, NF-κB phospho-p65 or phospho-IκBα. Taken together, these findings indicate that takinib inhibits inflammation in these cells by targeting multiple signaling pathways, most notably the JAK/STAT pathway in human RASFs.

Social media is ubiquitous and holds a significant place in modern society. Social media feeds are inundated with political content and are used by politicians and citizens alike to post political commentary. Neither mass media nor politics are new areas of study in sociology, but the entanglement of the two is proving to be of interest, as some scholarship argues that social media is driving changes in how politics works in the United States. We must consider how the citizenry consumes and processes political information in the modern era in view of the interplay between social media and current events. This study examines how membership and/or regular use of Facebook, and membership and/or regular use of Twitter affects perceived political understanding. I propose that, respectively, Facebook and Twitter use will increase perception of political understanding. Analysis of data from the 2016 General Social Survey reveals that Twitter membership and/or regular use is correlated with political understanding; meaning that those who use Twitter are more likely to believe they have an understanding of the political issues facing our country. The data confirms that the relationship between social media and political understanding must be taken seriously, and warrants deeper exploration. There is a need for future research that explores the kinds of content individuals consume on social media and the time they spend on these sites in order to develop a more robust understanding of exactly how social media use affects political understanding