Abstract |
IL-9 has lent its numerical designation to the Th9 subset of CD4+ Th cells, although it is also produced by additional cell types, including mast cells. It is a pleiotropic cytokine involved in allergic reactions, parasitic infections, autoimmune inflammation, and cancer immunity. In this article, we provide evidence that NFATc2 has contradictory functions in the expression of IL-9 in murine Th9 cells and bone marrow-derived mast cells (BMMC). The basis for this is our observation that the production of IL-9 in NFATc2-deficient Th9 cells is increased, whereas it is decreased in BMMC devoid of NFATc2. In addition, NFATc2 deficiency almost completely abrogates the expression of IL-3 in both cell types. However, selectively in BMMC, the production of IL-9 critically depends on autocrine IL-3 acting via the sustained activation of STAT5 on the expression of IL-9. Furthermore, we demonstrate that IL-3 acts independently and synergistically with IL-1β on the production of IL-9. Taken together, we highlight NFATc2-driven production of autocrine IL-3 as a critical and cell type-specific component for IL-9 expression in BMMC.
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Authors | Farhad Sabbaghi, Lorenz Ullner, Toszka Bohn, Jennifer Hahlbrock, Tobias Bopp, Edgar Schmitt, Matthias Klein, Michael Stassen |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 206
Issue 1
Pg. 67-76
(01 01 2021)
ISSN: 1550-6606 [Electronic] United States |
PMID | 33268486
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 by The American Association of Immunologists, Inc. |
Chemical References |
- Interleukin-3
- Interleukin-9
- NFATC Transcription Factors
- STAT5 Transcription Factor
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Topics |
- Animals
- Autocrine Communication
- Cells, Cultured
- Feedback, Physiological
- Interleukin-3
(metabolism)
- Interleukin-9
(genetics, metabolism)
- Mast Cells
(immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- NFATC Transcription Factors
(genetics, metabolism)
- STAT5 Transcription Factor
(metabolism)
- T-Lymphocytes, Helper-Inducer
(immunology)
- Up-Regulation
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