Editors' ChoiceImmunology

DCs in the Driver’s Seat

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Science Translational Medicine  06 Feb 2013:
Vol. 5, Issue 171, pp. 171ec23
DOI: 10.1126/scitranslmed.3005800

Efforts to understand the pathogenesis of autoimmune diseases have centered largely on effector T cells—T cells that differentiate to produce proinflammatory cytokines such as interleukin 17 (IL-17). The nature of how these T cells are driven to become inflammatory effectors is less characterized. Dendritic cells (DCs) are rare, highly potent antigen-presenting cells specialized to prime CD4+ and CD8+ T cells. Dendritic cells may originate in the setting of inflammation from monocytes but are also present in the steady state. In humans, studies have begun to identify inflammatory DCs in the setting of autoimmune and inflammatory diseases, such as psoriasis. Now, Segura and colleagues provide a robust characterization of human inflammatory DCs in inflammatory fluids that can drive CD4+ T cells to become interleukin-17–producing effector cells; this process is central to the pathogenesis of multiple autoimmune diseases.

The authors analyze the content of synovial fluid from patients with rheumatoid arthritis as well as inflammatory tumor ascites from cancer patients. Within CD11c and human lymphocyte antigen (HLA)–DR+ cells, they noticed a subset that were BDCA1+ and had dendrites, the property for which DCs were originally named. In contrast to CD16+ BDCA1 cells, this population could perform more robustly in the allogeneic mixed leukocyte reaction and were termed “inflammatory DCs.” These cells were not present in noninvaded lymphoid tissue (unaffected lymph nodes or tonsils from healthy volunteers) but were present in the spleens of gastric but not pancreatic cancer patients. Transcriptional analysis revealed expression of genes associated with both DCs and macrophage development, including expression of some key DC genes for DC differentiation. GeneSets and signatures of monocyte-derived DCs were enriched in the inflammatory DC subset, as compared with those of inflammatory macrophages or blood BDCA1+ DCs. Inflammatory DCs, but not macrophages isolated from ascites, cultured with T cells could drive T helper 17 (TH17) T cell polarization and secreted IL-23, a cytokine associated with TH17 polarization.

TH17 T cells have been implicated in the pathogenesis of multiple autoimmune and inflammatory conditions, including rheumatoid arthritis, psoriasis, multiple sclerosis, asthma, and inflammatory bowel disease. Now, inflammatory DCs isolated from pathogenic sites may drive these effector T cells and represent a therapeutic target for intervention and prevention.

E. Segura et al., Human inflammatory dendritic cells induce Th17 cell differentiation. Immunity, published online 22 January 2013 (10.1016/j.immuni.2012.10.018). [Abstract]

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