Cytokine signals through PI-3 kinase pathway modulate Th17 cytokine production by CCR6+ human memory T cells
Autor: | Ivana M. Djuretic, Thaddeus J. Carlson, Derya Unutmaz, Qi Wan, Lina Kozhaya, Mark S. Sundrud, Aimee ElHed, Radha Ramesh |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Receptors
CCR6 endocrine system medicine.medical_treatment T cell Immunology chemical and pharmacologic phenomena Biology Article Autoimmune Diseases Interleukin 22 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Aldesleukin medicine Immunology and Allergy Animals Humans IL-2 receptor 030304 developmental biology Inflammation Mice Knockout 0303 health sciences hemic and immune systems 3. Good health Cell biology Cytokine medicine.anatomical_structure Chronic Disease Cytokines Th17 Cells Ectopic expression Interleukin 17 Signal transduction Immunologic Memory Proto-Oncogene Proteins c-akt 030215 immunology Signal Transduction |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
Popis: | PI-3K–mediated repression of FOXO1 and KLF2 promotes proinflammatory cytokine expression by lineage-committed human CCR6+ Th17/Th22 memory cells. Human memory T cells (TM cells) that produce IL-17 or IL-22 are currently defined as Th17 or Th22 cells, respectively. These T cell lineages are almost exclusively CCR6+ and are important mediators of chronic inflammation and autoimmunity. However, little is known about the mechanisms controlling IL-17/IL-22 expression in memory Th17/Th22 subsets. We show that common γ chain (γc)–using cytokines, namely IL-2, IL-7, and IL-15, potently induce Th17-signature cytokine expression (Il17a, Il17f, Il22, and Il26) in CCR6+, but not CCR6−, TM cells, even in CCR6+ cells lacking IL-17 expression ex vivo. Inhibition of phosphoinositide 3-kinase (PI-3K) or Akt signaling selectively prevents Th17 cytokine induction by γc-cytokines, as does ectopic expression of the transcription factors FOXO1 or KLF2, which are repressed by PI-3K signaling. These results indicate that Th17 cytokines are tuned by PI-3K signaling in CCR6+ TM cells, which may contribute to chronic or autoimmune inflammation. Furthermore, these findings suggest that ex vivo analysis of IL-17 expression may greatly underestimate the frequency and pathogenic potential of the human Th17 compartment. |
Databáze: | OpenAIRE |
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