Abstract
Interleukin 4 (IL-4) and IL-13 are critical for responses to parasitic helminthes. We used genetically engineered reporter mice to assess the temporal and spatial production of these cytokines in vivo. In lymph nodes, IL-4, but not IL-13, was made by follicular helper T cells (TFH cells). In contrast, tissue type 2 helper T cells (TH2 cells) produced both cytokines. There was also divergent production of IL-4 and IL-13 among cells of the innate immune system, whereby basophils produced IL-4, whereas innate helper type 2 cells (Ih2 cells) produced IL-13. IL-13 production by TH2 and Ih2 cells was dependent on the transcription factor GATA-3, which was present in large amounts in these cells, and in contrast to the small amount of GATA-3 in TFH cells and basophils. The distinct localization and cellular expression of IL-4 and IL-13 explains their unique roles during allergic immunity.
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Acknowledgements
We thank G. Kelsoe (Duke University) for the anti-NP IgG1 clone H33Lγ1/λ1; the US National Institutes of Health Tetramer Core for reagents; A. McKenzie (University of Cambridge, UK) and Z. Werb (University of California San Francisco) for mice; D. Ehrle and M. Ansel for review and comments; and N. Flores and Z. Wang for technical expertise. Supported by the National Institutes of Allergy and Infectious Diseases (AI026918, AI030663 and AI077439), the Howard Hughes Medical Institute and the Sandler Asthma Basic Research Center at the University of California San Francisco.
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H.-E.L., R.L.R. and R.M.L. conceived of the work; H.-E.L. generated IL-13 reporter mice; H.-E.L., R.L.R., J.K.B. and B.M.S. designed and/or did experiments; I.-C.H. contributed reagents; R.L.R. and R.M.L. wrote the manuscript.
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Liang, HE., Reinhardt, R., Bando, J. et al. Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nat Immunol 13, 58–66 (2012). https://doi.org/10.1038/ni.2182
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DOI: https://doi.org/10.1038/ni.2182
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