- Published: October 3, 2022
- Updated: October 3, 2022
- University / College: University of Washington
- Language: English
- Downloads: 16
Editorial on the Research Topic
Immunomodulatory Functions of Fibroblast-like Synoviocytes in Joint Inflammation and Destruction during Rheumatoid Arthritis
Rheumatoid Arthritis (RA) is a common rheumatic disorder characterized by persistent synovial inflammation and destruction of joints. Fibroblast-like synoviocytes (FLSs) exhibit critical immunomodulatory functions through secretion of inflammatory cytokines and through direct interactions with several synovial-infiltrated immune cell types ( 1 , 2 ). RA FLSs also display surprisingly aggressive behavior ( 3 ), metabolic changes ( 4 , 5 ), and epigenetic alterations ( 6 , 7 ). More interestingly, recent studies have identified and described the biological functions of distinct subclasses of RA FLSs, for instance, FAPα + THY1 − fibroblasts are responsible for bone and cartilage damage, whereas FAPα + THY1 + fibroblasts mediate synovial inflammation ( 8 ). Another study indicates that THY1 + HLA-DRA hi fibroblasts contribute to IL-6 expression ( 9 ). Increasing evidence suggests that targeting activated FLS may be a novel therapeutic strategy for attenuating RA joint damage ( 3 ). This Research Topic brings together original and review articles that explore the immunomodulatory functions of FLS in joint inflammation and destruction in RA.
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3. Bottini N, Firestein GS. Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nat Rev Rheumatol.(2013) 9: 24–33. doi: 10. 1038/nrrheum. 2012. 190
4. McGarry T, Fearon U. Cell metabolism as a potentially targetable pathway in RA. Nat Rev Rheumatol . (2019) 15: 70–2. doi: 10. 1038/s41584-018-0148-8
5. Zou Y, Zeng S, Huang M, Qiu Q, Xiao Y, Shi M, et al. Inhibition of 6-phosphofructo-2-kinase suppresses fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis. Br J Pharmacol.(2017) 174: 893–908. doi: 10. 1111/bph. 13762
6. Zou Y, Xu S, Xiao Y, Qiu Q, Shi M, Wang J, et al. Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation. J Clin Invest.(2018) 128: 4510–24. doi: 10. 1172/JCI97965
7. Mo BY, Guo XH, Yang MR, Liu F, Bi X, Liu Y, et al. Long non-coding RNA GAPLINC promotes tumor-like biologic behaviors of fibroblast-like synoviocytes as MicroRNA sponging in rheumatoid arthritis patients. Front Immunol.(2018) 9: 702. doi: 10. 3389/fimmu. 2018. 00702
8. Croft AP, Campos J, Jansen K, Turner JD, Marshall J, Attar M, et al. Distinct fibroblast subsets drive inflammation and damage in arthritis Nature . (2019) 570: 246–51. doi: 10. 1038/s41586-019-1263-7
9. Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol.(2019) 20: 928–42. doi: 10. 1038/s41590-019-0378-1
10. Luo Y, Zheng SG. Hall of fame among pro-inflammatory cytokines: interleukin-6 gene and its transcriptional regulation mechanisms. Front Immunol.(2016) 7: 604. doi: 10. 3389/fimmu. 2016. 00604
