IL‐9 exerts biological function on antigen‐experienced murine T cells and exacerbates colitis induced by adoptive transfer. Issue 7 (18th March 2020)

• Record Type: Journal Article
• Authors: de Heusch, Magali; Steenwinckel, Valérie; Cochez, Perrine M.; Louahed, Jamila; Warnier, Guy; Lemaire, Muriel M.; Renauld, Jean‐Christophe; Dumoutier, Laure
• Is Part Of: European journal of immunology. Volume 50:Issue 7(2020)
• Page Start: 1034
• Page End: 1043
• Publication Date: 2020-03-18
• Subjects: adoptive transfer -- colitis -- IL‐9 -- Th2 -- Th17; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201948430
• Languages: English
• ISSNs: 0014-2980

Abstract

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 + CD45RB high 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 + CD45RB high T cells from WT but not from Il9r −/− mice, indicating that IL‐9 acts directly on T cells. Suprisingly, such naïve CD4 + CD45RB high T cells failed to express the Il9r or respond to IL‐9 in vitro, in contrast with CD4 + CD45RB low 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. Abstract : IL‐9 does not act on naïve T cells (CD45RB high cells or OVA‐specific T cells) but IL‐9 responsiveness is acquired by CD4 + T cells, more specifically TH2 and TH17, after in vivo activation and acquisition of CD44. Moreover, Il‐9r expression is required on T cells to induce colitis by adoptive transfer.