User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

TGF-beta interactions with IL-1 family members trigger IL-4-independent IL-9 production by mouse CD4(+) T cells

Primary tabs

Uyttenhove, Catherine [UCL] Brombacher, Frank Van Snick, Jacques [UCL]

TGF-beta and IL-4 were recently shown to selectively upregulate IL-9 production by nave CDC+ T cells. We report here that TGF-beta interactions with IL-1 alpha, IL-1 beta, IL-18, and IL-33 have equivalent IL-9-stimulating activities that function even in IL-4-deficient animals. This was observed after in vitro antigenic stimulation of immunized or unprimed mice and after polyclonal T-cell activation. Based on intracellular IL-9 staining, all IL-9-producing cells were CD4(+) and 80-90% had proliferated, as indicated by reduced CFSE staining. In contrast to IL-9, IL-13 and IL-17 were strongly stimulated by IL-1 and either inhibited (IL-13) or were unaffected (IL-17) by addition of TGF-beta. IL-9 and IL-17 production also differed in their dependence on IL-2 and regulation by IL-1/IL-23. As IL-9 levels were much lower in Th2 and Th17 cultures, our results identify TGF-beta/IL-1 and TGF-beta/IL-4 as the main control points of IL-9 synthesis.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2010
Language Anglais
Journal information "European Journal of Immunology" - Vol. 40, no. 8, p. 2230-2235 (2010)
Peer reviewed yes
Publisher Wiley-v C H Verlag Gmbh (Weinheim)
issn 0014-2980
e-issn 1521-4141
Publication status Publié
Affiliation UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
Keywords IL-1 family ; IL-9 regulation ; TGF-beta
Links
  1. Uyttenhove C., Simpson R. J., Van Snick J., Functional and structural characterization of P40, a mouse glycoprotein with T-cell growth factor activity., 10.1073/pnas.85.18.6934
  2. Schmitt Edgar, Brandwijk Renate Van, Snick Jacques Van, Siebold Bernhard, Rüde Erwin, Tcgfiii/p40 is produced by naive murine cd4+ t cells but is not a general t cell growth factor*, 10.1002/eji.1830191130
  3. Hültner Lothar, Druez Catherine, Moeller Jochen, Uyttenhove Catherine, Schmitt Edgar, Rüde Erwin, Dörmer Peter, van Snick Jacques, Mast cell growth-enhancing activity (MEA) is structurally related and functionally identical to the novel mouse T cell growth factor P40/TCGFIII (interleukin 9), 10.1002/eji.1830200632
  4. Richard M., Grencis R. K., Humphreys N. E., Renauld J.-C., Van Snick J., Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice, 10.1073/pnas.97.2.767
  5. Townsend Michael J, Fallon Padraic G, Matthews David J, Smith Philip, Jolin Helen E, McKenzie Andrew N.J, IL-9-Deficient Mice Establish Fundamental Roles for IL-9 in Pulmonary Mastocytosis and Goblet Cell Hyperplasia but Not T Cell Development, 10.1016/s1074-7613(00)00056-x
  6. Else, Immunology, 75, 232 (1992)
  7. Gessner André, Blum Horst, Röllinghoff Martin, Differential Regulation of IL-9-Expression after Infection with Leishmania major in Susceptible and Resistant Mice, 10.1016/s0171-2985(11)80414-6
  8. Gounni Abdelilah Soussi, Nutku Esra, Koussih Latifa, Aris Fadi, Louahed Jamila, Levitt Roy C., Nicolaides Nicholas C., Hamid Qutayba, IL-9 expression by human eosinophils: Regulation by IL-1β and TNF-α, 10.1067/mai.2000.109172
  9. Veldhoen Marc, Uyttenhove Catherine, van Snick Jacques, Helmby Helena, Westendorf Astrid, Buer Jan, Martin Bruno, Wilhelm Christoph, Stockinger Brigitta, Transforming growth factor-β 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9–producing subset, 10.1038/ni.1659
  10. Dardalhon Valérie, Awasthi Amit, Kwon Hyoung, Galileos George, Gao Wenda, Sobel Raymond A, Mitsdoerffer Meike, Strom Terry B, Elyaman Wassim, Ho I-Cheng, Khoury Samia, Oukka Mohamed, Kuchroo Vijay K, IL-4 inhibits TGF-β-induced Foxp3+ T cells and, together with TGF-β, generates IL-9+ IL-10+ Foxp3− effector T cells, 10.1038/ni.1677
  11. Schmitt, J. Immunol., 153, 3989 (1994)
  12. Bettelli Estelle, Carrier Yijun, Gao Wenda, Korn Thomas, Strom Terry B., Oukka Mohamed, Weiner Howard L., Kuchroo Vijay K., Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells, 10.1038/nature04753
  13. Mangan Paul R., Harrington Laurie E., O'Quinn Darrell B., Helms Whitney S., Bullard Daniel C., Elson Charles O., Hatton Robin D., Wahl Sharon M., Schoeb Trenton R., Weaver Casey T., Transforming growth factor-β induces development of the TH17 lineage, 10.1038/nature04754
  14. Veldhoen Marc, Hocking Richard J., Atkins Christopher J., Locksley Richard M., Stockinger Brigitta, TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells, 10.1016/j.immuni.2006.01.001
  15. Elyaman W., Bradshaw E. M., Uyttenhove C., Dardalhon V., Awasthi A., Imitola J., Bettelli E., Oukka M., van Snick J., Renauld J.-C., Kuchroo V. K., Khoury S. J., IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells, 10.1073/pnas.0812530106
  16. Nowak Elizabeth C., Weaver Casey T., Turner Henrietta, Begum-Haque Sakhina, Becher Burkhard, Schreiner Bettina, Coyle Anthony J., Kasper Lloyd H., Noelle Randolph J., IL-9 as a mediator of Th17-driven inflammatory disease, 10.1084/jem.20090246
  17. Helmby Helena, Grencis Richard?K., Interleukin 1 plays a major role in the development of Th2-mediated immunity, 10.1002/eji.200425452
  18. Humphreys Neil E., Grencis Richard K., IL-1-dependent, IL-1R1-independent resistance to gastrointestinal nematodes, 10.1002/eji.200838938
  19. von Stebut Esther, Ehrchen Jan M., Belkaid Yasmine, Kostka Susanna Lopez, Mölle Katharina, Knop Jürgen, Sunderkötter Cord, Udey Mark C., Interleukin 1α Promotes Th1Differentiation and Inhibits Disease Progression inLeishmania major–susceptible BALB/c Mice, 10.1084/jem.20030159
  20. Schmitt, J. Immunol., 147, 3848 (1991)
  21. Laurence Arian, Tato Cristina M., Davidson Todd S., Kanno Yuka, Chen Zhi, Yao Zhengju, Blank Rebecca B., Meylan Françoise, Siegel Richard, Hennighausen Lothar, Shevach Ethan M., O'Shea John J., Interleukin-2 Signaling via STAT5 Constrains T Helper 17 Cell Generation, 10.1016/j.immuni.2007.02.009
  22. Sutton Caroline, Brereton Corinna, Keogh Brian, Mills Kingston H.G., Lavelle Ed C., A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis, 10.1084/jem.20060285
  23. Murphy K., Heimberger A., Loh D., Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo, 10.1126/science.2125367
  24. Noben-Trauth Nancy, Köhler Georges, Bürki Kurt, Ledermann Birgit, Efficient targeting of the IL-4 gene in a BALB/c embryonic stem cell line, 10.1007/bf01980214
  25. Billiau Alfons, Heremans Hubertine, Vandekerckhove Filip, Dillen Chris, Anti-interferon-γ antibody protects mice against the generalized Shwartzman reaction, 10.1002/eji.1830171228
Bibliographic reference Uyttenhove, Catherine ; Brombacher, Frank ; Van Snick, Jacques. TGF-beta interactions with IL-1 family members trigger IL-4-independent IL-9 production by mouse CD4(+) T cells. In: European Journal of Immunology, Vol. 40, no. 8, p. 2230-2235 (2010)
Permanent URL http://hdl.handle.net/2078.1/33566