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NFκB attenuates IL-5 production and upregulates T-box transcription factors in Th2-like T cells

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Abstract

IL-5 plays important roles in eosinophil differentiation, expansion, and recruitment. The regulation of IL-5 seems critical for the treatment of eosinophil-mediated allergic reactions. However, the precise mechanisms for IL-5 regulation remain unknown. In this study, we investigated how IL-5 production is regulated. The transduction of GATA-3 into a murine T cell hybridoma resulted in acquiring the ability to produce IL-5 in response to an antigenic stimulus like Th2 cells. This production was dependent on the cAMP-PKA pathway, but not on p38 activation. Transduction of NIK largely impaired IL-5 production. RelA and RelB similarly impaired IL-5 production. RelA decreased not only IL-5 protein amount but mRNA. RelA also inhibited Il5-luciferase reporter activity. The transduction of GATA-3 decreased the expression of Tbx21 and Eomes, but the additional transduction of RelA abrogated the decreased expression of GATA-3-induced Tbx21 and Eomes. Furthermore, the transduction of T-bet or Eomes into the GATA-3-transduced T cell hybridoma impaired IL-5 production. These results suggested that strong enhancement of the NFκB pathway downregulates IL-5 production and upregulates T-box protein expression to shift an immune response from Th2 to inflammatory Th1.

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Acknowledgments

We thank to Dr. T. Kitamura, Institute of Medical Science, the University of Tokyo, for providing the retroviral vector pMXs-IG and packaging cell, PLAT-E; Dr. T. Nakayama, Chiba University, for providing IκBαM, the repressor mutant of IκBα and the retroviral vector pMXs-IRES-hNGFR and for transferring OT-II mice; Dr. William R. Heath, The Walter and Eliza Hall Institute of Medical Research, for providing the OT-II mice; Ms. Y. Nonaka for cell sorting; Ms. Y. Nitta for secretary assistance. This study was in part supported by a Grant-in-aid by the Japan Society for the Promotion of Science (24580196) and by a grant from the Minato Seki Foundation.

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  1. Department of Immunology, School of Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan

    Masaaki Hashiguchi, Ayano Kobayashi, Yuji Kashiwakura, Hidefumi Kojima, Yumiko Kanno & Tetsuji Kobata

  2. Department of Legal Medicine, School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan

    Akira Kurosu & Shogo Tokudome

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  1. Masaaki Hashiguchi
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Correspondence to Masaaki Hashiguchi.

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Hashiguchi, M., Kobayashi, A., Kashiwakura, Y. et al. NFκB attenuates IL-5 production and upregulates T-box transcription factors in Th2-like T cells. Cytotechnology 66, 373–382 (2014). https://doi.org/10.1007/s10616-013-9585-z

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