Enriched CD141+ DCs in the joint are transcriptionally distinct, activated, and contribute to joint pathogenesis.
Item Type:Journal Article
Citation:Canavan M, Walsh AM, Bhargava V, Wade SM, McGarry T, Marzaioli V, Moran B, Biniecka M, Convery H, Wade S, Orr C, Mullan R, Fletcher JM, Nagpal S, Veale DJ, Fearon U, Enriched CD141+ DCs in the joint are transcriptionally distinct, activated, and contribute to joint pathogenesis., JCI Insight, 3, 23, 2018, 95228-
CD141+ DC are implicated in antiviral and antitumor immunity. However, mechanisticstudies in autoimmune disease are limited. This is the first study to our knowledgeexamining CD141+ DC in autoimmune disease, specifically inflammatory arthritis (IA). Weidentified significant enrichment of CD141+ DC in the inflamed synovial joint, which weretranscriptionally distinct from IA and healthy control (HC) blood CD141+ DC andsignificantly more activated, and they exhibited increased responsiveness to TLR3.Synovial CD141+ DC represent a bone fide CD141+ DC population that is distinct fromCD1c+ DC. Synovial CD141+ DC induced higher levels of CD4+ and CD8+ T cell activationcompared with their peripheral blood counterparts, as made evident by expression of IFN-g,TNF-a, and granulocyte-macrophage CSF (GMCSF). Autologous synovial CD141+ DCcocultures also induce higher levels of these cytokines, further highlighting their contributionto synovial inflammation. Synovial CD141+ DC–T cell interactions had the ability to furtheractivate synovial fibroblasts, inducing adhesive and invasive pathogenic mechanisms.Furthermore, we identify a mechanism in which synovial CD141+ DC are activated, vialigation of the hypoxia-inducible immune-amplification receptor TREM-1, which increasedsynovial CD141+ DC activation, migratory capacity, and proinflammatory cytokines. Thus,synovial CD141+ DC display unique mechanistic and transcriptomic signatures, which aredistinguishable from blood CD141+ DC and can contribute to synovial joint inflammation.
Type of material:Journal Article
Series/Report no:JCI Insight
Availability:Full text available
Keywords:Dendritic Cells, T-Lymphocytes, Plasmacytoid DCs, Autoimmunity, Dendritic cells, Immunology
Subject (TCD):Immunology, Inflammation & Infection , Autoimmune Diseases (Multiple Sclerosis, Rheumatoid Arthritis) , HUMAN DENDRITIC CELLS