IL-2 Shapes the Survival and Plasticity of IL-17–Producing γδ T Cells
| Autor: | Daniel Christ, Rodrigo Vazquez-Lombardi, Jonathan Sprent, Cecile King, Jessica Stolp, Robert Brink, Joanna Warren, Kylie E. Webster, Theresa M. Corpuz, Jason K. Luong |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival T-Lymphocytes medicine.medical_treatment Immunology Inflammation Biology Interleukin-23 Interferon-gamma Mice 03 medical and health sciences Immune system Downregulation and upregulation medicine Animals Immunology and Allergy IL-2 receptor Cell Proliferation Receptors Interleukin-7 Interleukin-17 T-cell receptor Cell Differentiation Receptors Antigen T-Cell gamma-delta Flow Cytometry In vitro Cell biology Mice Inbred C57BL 030104 developmental biology Cytokine Cytokines Interleukin-2 Positive Regulatory Domain I-Binding Factor 1 Interleukin 17 medicine.symptom Signal Transduction Transcription Factors |
| Zdroj: | The Journal of Immunology. 199:2366-2376 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1700335 |
| Popis: | IL-17–producing γδ T (γδT-17) cells have proved to be an important early source of IL-17 in many inflammatory settings and are emerging as an important participant in protumor immune responses. Considering that their peripheral activation depends largely on innate signals rather than TCR ligation, it is important to understand what mechanisms exist to curb unwanted activation. Expression of the high-affinity IL-2R on γδT-17 cells prompted us to investigate a role for this cytokine. We found γδT-17 cells to be enriched, not depleted, in IL-2–deficient mice. The absence of IL-2 also resulted in higher IL-17 production and the emergence of IL-17+IFN-γ+ double producers. Furthermore, the addition of IL-2 to in vitro cultures of sorted γδT-17 cells was able to moderate IL-17 and affect differentiation into polyfunctional cytokine-producing cells. Interestingly, the Vγ6+ subset was more susceptible to the effects of IL-2 than Vγ4+ γδT-17 cells. We also found that unlike other γδ T cells, γδT-17 cells do not produce IL-2, but express Blimp-1, a known transcriptional repressor of IL-2. Although IL-2 was able to induce robust proliferation of γδT-17 cells, it did not sustain viability, negatively impacting their survival via downregulation of the IL-7R. Taken together, these data indicate that IL-2 can augment the γδT-17 response in favor of short-lived effectors with limited plasticity, particularly in the presence of IL-1β and IL-23. In this way, IL-2 may act to curtail the innate-like response of γδT-17 cells upon arrival of IL-2–producing adaptive immune cells at the site of inflammation. |
| Databáze: | OpenAIRE |
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