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The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses

Nature Immunology volume 14, pages 364–371 (2013)Cite this article

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A Corrigendum to this article was published on 18 February 2014

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Abstract

Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T helper type 2 (TH2), but not TH1, allergic responses in both the skin and lungs. Loss of STAT5 in DCs led to the inability to respond to thymic stromal lymphopoietin (TSLP). STAT5 was required for TSLP-dependent DC activation, including upregulation of the expression of costimulatory molecules and chemokine production. Furthermore, TH2 responses in mice with DC-specific loss of STAT5 resembled those seen in mice deficient in the receptor for TSLP. Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces.

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Figure 1: Diminished TH2 CHS Cre+Stat5fl/fl mice.
Figure 2: Normal TH1-type CHS in Cre+Stat5fl/fl mice.
Figure 3: STAT5 is not required in LCs for TH2-type CHS.
Figure 4: TH2- but not TH1-type immune responses in the lungs require STAT5 in DCs.
Figure 5: STAT5 is required for TSLP-induced upregulation of the expression of costimulatory molecules in FL-CD11b-DCs.
Figure 6: TSLP-induced STAT5 in DCs is required for the TH2 differentiation of CD4+ T cells.

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  • 23 September 2013

    In the version of this article initially published, author Daniel H. Kaplan was not included. The correct list of authors and affiliations is as follows: 1Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA. 2Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA. 3Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA. 4Center for Immunology, Department of Dermatology, University of Minnesota, Minneapolis, Minnesota, USA. 5Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA. 6Laboratory of Genetics and Physiology, US National Institutes of Health, Bethesda, Maryland, USA. 7These authors contributed equally to this work. Correspondence should be addressed to S.F.Z. (sziegler@benaroyaresearch.org). The Acknowledgments section should not include the first acknowledgement and should begin "We thank I. Förster..."; the Author Contributions section should include Daniel H. Kaplan's contributions as follows: "D.H.K., K.S., K.-U.W., B.R. and L.H. provided mouse strains and expertise;...." The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank I. Förster (University of Bonn) for mice with a transgene encoding GFP in the Ccl17 locus; T. Nakayama (Chiba University) for pMX-Cre-IRES-GFP; D. Rawlings and H. Kerns (Seattle Children's Research Institute) for Btk- and Tec-deficient bone marrow; J. Hamerman and D. Campbell for discussions of the manuscript; S. Ma and W. Xu for technical support; and M. Warren and S. McCarty for administrative support. Supported by the US National Institutes of Health (R01-AI068731, R01-AR056113, R01-AR055695 and P01-HL098067 to S.F.Z., and 5T32AI007411-19 to B.D.B.).

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Author notes

  1. Bryan D Bell and Masayuki Kitajima: These authors contributed equally to this work.

Authors and Affiliations

  1. Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA

    Bryan D Bell, Masayuki Kitajima, Ryan P Larson, Thomas A Stoklasek, Kristen Dang & Steven F Ziegler

  2. Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA

    Bryan D Bell, Masayuki Kitajima, Ryan P Larson, Thomas A Stoklasek & Steven F Ziegler

  3. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Kazuhito Sakamoto & Kay-Uwe Wagner

  4. Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA

    Daniel H Kaplan

  5. Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA

    Boris Reizis

  6. Laboratory of Genetics and Physiology, US National Institutes of Health, Bethesda, Maryland, USA

    Lothar Hennighausen

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Contributions

B.D.B. and M.K. did most of the experiments and wrote the manuscript, with help from S.F.Z.; D.H.K., K.S., K.-U.W., B.R. and L.H. provided mouse strains and expertise; R.P.L. collaborated on the CHS studies; T.A.S. did the influenza infections and analyzed the response to infection; K.D. provided help with bioinformatics; and S.F.Z. supervised the work.

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Correspondence to Steven F Ziegler.

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Bell, B., Kitajima, M., Larson, R. et al. The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses. Nat Immunol 14, 364–371 (2013). https://doi.org/10.1038/ni.2541

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