Independent molecular control of IL-17 and IL-22 in the human Th17 response
Franca
Gerosa1*,
Marco
Cardone2,
Lisa
Provezza1,
Elisa
Zoratti1,
Ornella
Poffe1,
Giovanna
Batoni3,
Amiran
Dzutsev2,
Ena
Wang4,
Michela
Conti1,
Rocco
Micciolo5,
Semih
Esin3,
Angelo
Cazzadori1,
Giuseppe
Carra1 and
Giorgio
Trinchieri2
-
1
Dipartimento di Patologia e Diagnostica Universita' di Verona, Italy
-
2
National Cancer Institute, Center for Cancer Research, United States
-
3
University of Pisa, Dipartimento di Ricerca Traslazionale e Nuove Tecnologie, Italy
-
4
National Institutes of Health, Department of Transfusion Medicine, United States
-
5
Universita' di Trento, Dipartimento di Sociologia e Ricerca Sociale, Italy
IL-17 and IL-22 are cytokines considered distinctive of Th17 cells and associately produced by such cells. To approach the problem of the relationship in the expression of IL-17 and of IL-22 we analyzed the production of these cytokines, as well as of IFN-g, in memory Th cells specific for Candida albicans, commonly regarded as a classic exemple of Th17 cells, or for M. tuberculosis, a pathogen which requires production of IFN-g for resolution of infection. Moreover, naïve CD4+ T cells were cultured in the presence of Th17-promoting mixture of IL-1β, IL-6 and IL-23 or supernatant from DCs stimulated with zymosan (SNDCzym), or perturbating these microenvironments using various combinations of IL-1β, IL-6 and IL-23, or with SNDCzym in which various combinations of IL-1β, IL-6, IL-12 and IL-23 have been neutralized using specific antibodies or IL-1RA.
Ex vivo, M. tuberculosis-specific memory Th cells express IFN-g, while IL-17 and IL-22 cells are virtually absent; candida-specific memory Th cells expressed consistent percentages IL-17, IL-22 or IFN-g, with a significant correlation between expression of IL-17 and IL-22 in different donors, suggesting a dependent expression of IL-17 and of IL-22 in these memory cells.
However, in naive Th cells, perturbation of the Th17-promoting microenvironments identified (a) an independent production of IL-17 and of IL-22, depending on the combination of the cytokines IL-6, IL-23 and IL-1, which played pivotal and sometimes opposing roles in the regulation of IL-17, IL-22 and IFN-g expression, (b) correlation profiles between Th effector cytokines and Th – associated genes, including transcriptional regulators.
Acknowledgements
The work was supported in part by Fondazione Cariverona and PRIN2008
Keywords:
Th17,
IL-22,
IFN-g,
memory Th cells,
naive Th cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Gerosa
F,
Cardone
M,
Provezza
L,
Zoratti
E,
Poffe
O,
Batoni
G,
Dzutsev
A,
Wang
E,
Conti
M,
Micciolo
R,
Esin
S,
Cazzadori
A,
Carra
G and
Trinchieri
G
(2013). Independent molecular control of IL-17 and IL-22 in the human Th17 response.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01126
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Received:
28 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Franca Gerosa, Dipartimento di Patologia e Diagnostica Universita' di Verona, Verona, Italy, franca.gerosa@univr.it