IL-9 exerts biological function on antigen-experienced murine T cells and exacerbates colitis induced by adoptive transfer |
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Authors: | Magali de Heusch Valérie Steenwinckel Perrine M. Cochez Jamila Louahed Guy Warnier Muriel M. Lemaire Jean-Christophe Renauld Laure Dumoutier |
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Affiliation: | 1. Experimental Medicine Unit, de Duve Institute, Université catholique de Louvain, Brussels, Belgium These authors contributed equally to this work.;2. Experimental Medicine Unit, de Duve Institute, Université catholique de Louvain, Brussels, Belgium |
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Abstract: | IL-9 is involved in various T cell-dependent inflammatory models including colitis, encepahlitis, and asthma. However, the regulation and specificity of IL-9 responsiveness by T cells during immune responses remains poorly understood. Here, we addressed this question using two different models: experimental colitis induced by transfer of naive CD4+CD45RBhigh T cells into immunodeficient mice, and OVA-specific T cell activation. In the colitis model, constitutive IL-9 expression exacerbated inflammation upon transfer of CD4+CD45RBhigh T cells from WT but not from Il9r−/− mice, indicating that IL-9 acts directly on T cells. Suprisingly, such naïve CD4+CD45RBhigh T cells failed to express the Il9r or respond to IL-9 in vitro, in contrast with CD4+CD45RBlow T cells. By using OVA-specific T cells, we observed that T cells acquired the capacity to respond to IL-9 along with CD44 upregulation, after long-lasting (5 to 12 days) in vivo antigenic stimulation. Il9r expression was associated with Th2 and Th17 phenotypes. Interestingly, in contrast to the IL-2 response, antigen restimulation downregulated IL-9 responsiveness. Taken together, our results demonstrate that IL-9 does not act on naïve T cells but that IL-9 responsiveness is acquired by CD4+ T cells after in vivo activation and acquisition of memory markers such as CD44. |
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Keywords: | adoptive transfer colitis IL-9 Th2 Th17 |
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