Human Th17 Cells Comprise Heterogeneous Subsets Including IFN-γ–Producing Cells with Distinct Properties from the Th1 Lineage
| Autor: | Mandy J. McGeachy, Bela Desai, Robert H. Pierce, Katia Boniface, Svetlana Sadekova, Terrill K. McClanahan, Katherine Brovont-Porth, Beth Basham, Rene de Waal Malefyt, Wendy M. Blumenschein |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_treatment
Immunology Cell Separation Immunophenotyping Interferon-gamma Interleukin 21 T-Lymphocyte Subsets medicine Humans Immunology and Allergy Cell Lineage IL-2 receptor Cells Cultured Interleukin 3 CD40 biology Gene Expression Profiling Interleukin-17 Th1 Cells Interleukin-12 Cell biology CCL20 Cytokine biology.protein Interleukin 12 Cytokines Inflammation Mediators |
| Zdroj: | The Journal of Immunology. 185:679-687 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Th17 cells have been named after their signature cytokine IL-17 and accumulating evidence indicates their involvement in the induction and progression of inflammatory diseases. In addition to IL-17 single-producing T cells, IL-17/IFN-γ double-positive T cells are found in significantly elevated numbers in inflamed tissues or blood from patients with chronic inflammatory disorders. Because IFN-γ is the classical Th1-associated cytokine, the origin and roles of these subsets remain elusive. In this paper, we show that not only IL-17+/IFN-γ+ but also IFN-γ+ (IL-17−) cells arise under Th17-inducing condition and have distinct properties from the Th1 lineage. In fact, these populations displayed characteristics reminiscent to IL-17 single-producing cells, including production of IL-22, CCL20, and induction of antimicrobial gene expression from epithelial cells. Live sorted IL-17+ and Th17–IFN-γ+ cells retained expression of IL-17 or IFN-γ after culture, respectively, whereas the IL-17+/IFN-γ+ population was less stable and could also become IL-17 or IFN-γ single-producing cells. Interestingly, these Th17 subsets became “Th1-like” cells in the presence of IL-12. These results provide novel insights into the relationship and functionality of the Th17 and Th1 subsets and have direct implications for the analysis and relevance of IL-17 and/or IFN-γ–producing T cells present in patients’ peripheral blood and inflamed tissues. |
| Databáze: | OpenAIRE |
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