Year: 2024
Type: editorial
Abstract: (https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1351446/full) investigate the possible association between type I IFN dysfunction and the disease state in asymptomatic individuals with antiphospholipid antibodies (aPL) and APS patients. SLE patients and healthy subjects without aPL are used as control groups. Seven interferon stimulated genes (ISGs) were evaluated in whole blood to produce a composite IFN score. Significant IFN activation was observed across the APS spectrum, although the exact level of the individual gene expression and the IFN score varied. This was found even in patients who did not meet the clinical criteria of APS but had persistently positive aPL. SLE patients displayed the highest and most consistent activation. Thrombosis reoccurrence was positively associated with certain ISGs in patients with secondary APS (having both APS and SLE). The elevated presence of ISGs in patients only having aPL may represent a potential biomarker to stratify high risk for thrombosis patients.An intriguing interplay of different type I interferons in cutaneous lupus erythematosus (CLE) was uncovered by Xu et al.(https://www.frontiersin.org/journals/lupus/articles/10.3389/flupu.2024.1359714/full ). The researchers had previously shown that IFN-κ was overexpressed in lesional and non-lesional CLE keratinocytes contributing to photosensitivity, but the key mechanisms for the reported IFN-κ production were unknown. After Poly (I:C) stimulation, keratinocytes rapidly produced IFN-β, but IFN-κ instead was only produced after a prolonged time delay. Blocking IFNAR only resulted in inhibiting IFN-κ. Similarly, inhibition of IFN-β decreased IFN-κ production. IFN-β knockout cell lines were incapable of producing IFN-κ after either Poly I:C or UVB stimulation. These results altogether demonstrate that IFN-κ is both an IFN gene and an IFN-simulated gene.The work of Xia et al. assesses the effect of losing a mechanism of chemokine degradation in a model of lupus nephritis (https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00691/full#B23). The atypical chemokine receptor 2 (ACKR2) is found in the afferent lymphatics of many human tissues and can bind most of the CC chemokines. Through the expression of ACKRs, lymphatic vessels regulate chemokine levels and immune cell migration. The researchers used blood and tissues from ACKR2deficient lupus-prone B6lpr and WTB6lpr mice to determine alterations to cellular patterns of inflammation and organ damage. In B6lpr mice that developed lupus nephritis, ACKR2 deficiency resulted in greater T and B cell tubulointerstitial inflammation, but these alterations were not associated with greater renal disease or higher levels of the assessed inflammatory mediators. These results show that the loss of ACKR2-mediated chemokine degradation can be compensated in vivo by other mechanisms.The combined work of all these papers demonstrates the value of intracellular signaling events to in vivo mechanisms further shedding light on the complexity of SLE.Wendy I. White, PhD Jilian M. Richmond, PhD Antonios Psarras, MD, PhD
Source: Frontiers in Lupus
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,125
OpenAlex ID: W4401977207