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Sustained signaling by canonical helper T cell cytokines throughout the reactive lymph node

Nature Immunology volume 11, pages 520–526 (2010)Cite this article

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Abstract

Cytokines are soluble proteins that regulate immune responses. The present paradigm is that cytokine production in lymphoid tissues is tightly localized and signaling occurs between conjugate cells. Here we assess cytokine signaling during infection by measuring in vivo phosphorylation of intracellular signal transducer and activator of transcription (STAT) proteins. We show that interferon-γ (IFN-γ) and interleukin 4 (IL-4) signaled to the majority of lymphocytes throughout the reactive lymph node and that IL-4 conditioning of naive, bystander cells was sufficient to override opposing T helper type 1 (TH1) polarization. Our results demonstrate that despite localized production, cytokines can permeate a lymph node and modify the majority of cells therein. Cytokine conditioning of bystander cells could provide a mechanism by which chronic worm infections subvert the host response to subsequent infections or vaccination attempts.

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Figure 1: IL-4 signals elicit STAT6 phosphorylation and IL-4R upregulation throughout a TH2-reactive lymph node.
Figure 2: IFN-γ signals permeate a TH1-reactive lymph node.
Figure 3: STAT6 phosphorylation occurs in draining but not nondraining lymphoid tissues.
Figure 4: STAT6 phosphorylation in the TH2-reactive lymph node is sustained and reflects continuous IL-4R triggering.
Figure 5: Estimation of the effective interstitial IL-4 concentration in the TH2-reactive lymph node.
Figure 6: IL-4 conditioning of naive lymphocytes alters subsequent helper T cell polarization.

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Acknowledgements

We thank L.L. Johnson for T. gondii infection; J.-S. Lin and S.T. Smiley (both with the Trudeau Institute) for heat-killed Y. pestis; E.J. Pearce (Trudeau Institute) for S. mansoni eggs; R.T. Robinson and A.M. Cooper (both with the Trudeau Institute) for Ifng−/− mice; and E.J. Pearce and D. Gray for discussion and comments on the manuscript. Supported by the Trudeau Institute and the National Institutes of Health (AI072296 and AI076479).

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  1. Trudeau Institute, Saranac Lake, New York, USA

    Georgia Perona-Wright, Katja Mohrs & Markus Mohrs

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  1. Georgia Perona-Wright
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G.P.-W. and M.M. designed the research and prepared the manuscript; G.P.-W. and K.M. did the experiments; G.P.-W. analyzed and interpreted the results; and M.M. guided the study.

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Correspondence to Markus Mohrs.

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Perona-Wright, G., Mohrs, K. & Mohrs, M. Sustained signaling by canonical helper T cell cytokines throughout the reactive lymph node. Nat Immunol 11, 520–526 (2010). https://doi.org/10.1038/ni.1866

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