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JCI Insight. 2018 Dec 6;3(23). pii: 95228. doi: 10.1172/jci.insight.95228. [Epub ahead of print]

Enriched Cd141+ DCs in the joint are transcriptionally distinct, activated, and contribute to joint pathogenesis.

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Molecular Rheumatology, School of Medicine, Trinity College Dublin, Ireland.
Immunology and.
Discovery Sciences, Janssen Research & Development, Spring House, Pennsylvania, USA.
School of Biochemistry and Immunology, Trinity College Dublin, Ireland.
Centre for Arthritis & Rheumatic Diseases, St. Vincent's University Hospital, University College Dublin, Ireland.
Department of Rheumatology, Adelaide and Meath Hospital, Dublin, Ireland.
Translational Immunology, Schools of Biochemistry and Immunology and Medicine, Trinity College Dublin, Ireland.


CD141+ DC are implicated in antiviral and antitumor immunity. However, mechanistic studies in autoimmune disease are limited. This is the first study to our knowledge examining CD141+ DC in autoimmune disease, specifically inflammatory arthritis (IA). We identified significant enrichment of CD141+ DC in the inflamed synovial joint, which were transcriptionally distinct from IA and healthy control (HC) blood CD141+ DC and significantly more activated, and they exhibited increased responsiveness to TLR3. Synovial CD141+ DC represent a bone fide CD141+ DC population that is distinct from CD1c+ DC. Synovial CD141+ DC induced higher levels of CD4+ and CD8+ T cell activation compared with their peripheral blood counterparts, as made evident by expression of IFN-γ, TNF-α, and granulocyte-macrophage CSF (GMCSF). Autologous synovial CD141+ DC cocultures also induce higher levels of these cytokines, further highlighting their contribution to synovial inflammation. Synovial CD141+ DC-T cell interactions had the ability to further activate synovial fibroblasts, inducing adhesive and invasive pathogenic mechanisms. Furthermore, we identify a mechanism in which synovial CD141+ DC are activated, via ligation of the hypoxia-inducible immune-amplification receptor TREM-1, which increased synovial CD141+ DC activation, migratory capacity, and proinflammatory cytokines. Thus, synovial CD141+ DC display unique mechanistic and transcriptomic signatures, which are distinguishable from blood CD141+ DC and can contribute to synovial joint inflammation.


Autoimmunity; Dendritic cells; Immunology

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