Anna Malecka
Stromal fibroblasts support dendritic cells to maintain IL-23/Th17 responses after exposure to ionizing radiation
Malecka, Anna; Wang, Ounwei; Shah, Sabaria; Sutavani, Ruhcha V.; Spendlove, Ian; Ramage, Judith M.; Greensmith, Julie; Franks, Hester A.; Gough, Michael J.; Saalbach, Anja; Patel, Poulam M.; Jackson, Andrew M.
Authors
Ounwei Wang
Sabaria Shah
Ruhcha V. Sutavani
IAN SPENDLOVE IAN.SPENDLOVE@NOTTINGHAM.AC.UK
Associate Professor
JUDITH RAMAGE JUDITH.RAMAGE@NOTTINGHAM.AC.UK
Associate Professor
JULIE GREENSMITH julie.greensmith@nottingham.ac.uk
Lecturer
HESTER FRANKS HESTER.FRANKS@NOTTINGHAM.AC.UK
Clinical Associate Professor/ anne Mclaren Fellowship
Michael J. Gough
Anja Saalbach
POULAM PATEL POULAM.PATEL@NOTTINGHAM.AC.UK
Professor of Clinical Oncology
ANDREW JACKSON ANDREW.JACKSON@NOTTINGHAM.AC.UK
Associate Professor
Abstract
Dendritic cell function is modulated by stromal cells, including fibroblasts. Although poorly understood, the signals delivered through this crosstalk substantially alter dendritic cell biology. This is well illustrated with release of TNF-0/IL-113 from activated dendritic cells, promoting PGE2 secretion from stromal fibroblasts. This instructs dendritic cells to up-regulate IL-23, a key Th17-polarizing cytokine. We previously showed that ionizing radiation inhibited IL-23 production by human dendritic cells in vitro. In the present study, we investigated the hypothesis that dendritic cell-fibroblast crosstalk over¬comes the suppressive effect of ionizing radiation to support appropriately polarized Th17 responses. Radia¬tion (1–6 Gy) markedly suppressed IL-23 secretion by activated dendritic cells (P < 0.0001) without adversely impacting their viability and consequently, inhibited the generation of Th17 responses. Cytokine suppression by ionizing radiation was selective, as there was no effect on IL-10, -6, -10, and -27 or TNF-a and only a modest (11%) decrease in IL-12p70 secretion. Coculture with fibroblasts augmented IL-23 secretion by irradiated dendritic cells and increased Th17 responses. Impor¬tantly, in contrast to dendritic cells, irradiated fibroblasts maintained their capacity to respond to TNF-0/IL-10 and produce PGE2, thus providing the key intermediary signals for successful dendritic cell-fibroblasts crosstalk. In summary, stromal fibroblasts support Th17-polarizing cytokine production by dendritic cells that would other¬wise be suppressed in an irradiated microenvironment. This has potential ramifications for understanding the immune response to local radiotherapy. These findings underscore the need to account for the impact of microenvironmental factors, including stromal cells, in understanding the control of immunity. J. Leukoc. Biol. 100: 000–000; 2016.
Citation
Malecka, A., Wang, O., Shah, S., Sutavani, R. V., Spendlove, I., Ramage, J. M., …Jackson, A. M. (2016). Stromal fibroblasts support dendritic cells to maintain IL-23/Th17 responses after exposure to ionizing radiation. Journal of Leukocyte Biology, 100(2), 381-389. https://doi.org/10.1189/jlb.3A1015-474R
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 18, 2016 |
Online Publication Date | Apr 5, 2016 |
Publication Date | 2016-08 |
Deposit Date | May 21, 2016 |
Publicly Available Date | May 21, 2016 |
Journal | Journal of Leukocyte Biology |
Print ISSN | 0741-5400 |
Electronic ISSN | 1938-3673 |
Publisher | Society for Leukocyte Biology |
Peer Reviewed | Peer Reviewed |
Volume | 100 |
Issue | 2 |
Pages | 381-389 |
DOI | https://doi.org/10.1189/jlb.3A1015-474R |
Public URL | https://nottingham-repository.worktribe.com/output/797852 |
Publisher URL | http://www.jleukbio.org/content/100/2/381 |
Contract Date | May 21, 2016 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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