Tc17 biology and function: Novel concepts

• Published in: European journal of immunology Vol. 50; no. 9; pp. 1257 - 1267
• Main Authors: Lückel, Christina, Picard, Felix. S. R., Huber, Magdalena
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-09-2020
• Subjects: Animal models; Animals; Arthritis; Autoimmune diseases; Autoimmunity; CD8 antigen; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; Cell differentiation; Effector cells; Gastrointestinal tract; Helper cells; Homeostasis; Humans; IL‐17; inflammation; Inflammatory diseases; Interleukin-17 - immunology; Lung diseases; Lung transplantation; Lymphocytes; Lymphocytes T; Mucosa; plasticity; Psoriasis; Rheumatic diseases; T-Lymphocyte Subsets - immunology; Tc17; Ulcerative colitis; CD8+ T cells; plasticity; Tc17; inflammation; IL-17
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202048627

Research over the past years has provided increasing understanding about IL‐17‐producing CD8+ T cells termed Tc17 or IL‐17+CD8+ T cells, their distribution and role in a range of diverse immune processes. These comprise resistance to pathogens and tissue homeostasis, but also contribution to autoimmunity and cancer, as well as involvement in gut inflammation, lung diseases and graft‐versus‐host‐disease. Tc17 cells are regulated by unique differentiation mechanisms distinguishing them from other IL‐17‐producing T cells, including Th17, mucosal‐associated invariant T cells, and γδ17 T cells, thus ensuring their specific function in immune responses. Here, we review recent advances in understanding Tc17 cell differentiation and function, and highlight experimental evidence from human studies on patients suffering from organ‐specific autoimmunity including psoriasis, spondyloarthritis and MS as well as from ulcerative colitis and gastrointestinal tract‐associated cancers. We also discuss mouse models analyzing Tc17 characteristics and indicate mechanisms of cross‐talk between Tc17 cells and immune or nonimmune cells, enabling their effector function in both protective as well as pathologic immune responses.
Tc17 cells are IL‐17‐producing CD8+ T cells with clear molecular differences to Th17, MAIT17, and γδ17 cells. Their plasticity toward CTL or Tc2 phenotype drives multifaceted cytokine production, allowing adaptation to environmental changes and contribution to protective immune responses, tissue homeostasis, as well as to autoimmunity, inflammatory diseases, and cancer.