Article | Published:

The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells

Nature Immunology volume 14, pages 446453 (2013) | Download Citation

  • An Erratum to this article was published on 19 July 2013

This article has been updated

Abstract

Spleen-resident dendritic cell (DC) populations occupy sentinel positions for the capture and presentation of blood-borne antigens. Here we found a difference in expression of the chemotactic receptor EBI2 (GPR183) on splenic DC subsets and that EBI2 regulated the positioning and homeostasis of DCs in the spleen. EBI2 and its main ligand, 7α,25-OHC, were required for the generation of the splenic CD4+ DC subset and the localization of DCs in bridging channels. Absence of EBI2 from DCs resulted in defects in both the activation of CD4+ T cells and the induction of antibody responses. Regulated expression of EBI2 on DC populations is therefore critical for the generation and correct positioning of splenic DCs and the initiation of immune responses.

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Change history

  • 22 April 2013

    In the version of this article initially published, the top graph in Figure 7g was incorrect. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank the MLC Garvan Flow Cytometry Facility for cell sorting; the staff of Australian Bioresources and the Garvan Institute animal facilities; and J. Villadangos, K. Shortman and S. Tangye for comments on the manuscript. Supported by the National Health and Medical Research Council of Australia (427620 to R.B. and 1003025 to D.G.)

Author information

Affiliations

  1. Immunological Diseases Division, Garvan Institute of Medical Research, Darlinghurst, Australia.

    • Dominique Gatto
    • , Katherine Wood
    • , Danielle Murphy-Durland
    • , Peter Schofield
    • , Daniel Christ
    •  & Robert Brink
  2. St. Vincent's Clinical School, University of New South Wales, Sydney, Australia.

    • Dominique Gatto
    • , Daniel Christ
    •  & Robert Brink
  3. Burnet Institute, Prahran, Australia.

    • Irina Caminschi
  4. Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, Australia.

    • Gunasegaran Karupiah

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Contributions

D.G. and R.B. conceived of the project and wrote the manuscript; D.G. and K.W. did most of the experiments; I.C. provided antibody to Sirpβ1 and analyzed anti-rat IgG responses; D.M.-D. produced and analyzed cells transfected to express EBI2; P.S. and D.C. organized the production and purification of antibody to EBI2; and G.K. helped analyze responses in EBI2-deficient mice.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Dominique Gatto or Robert Brink.

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DOI

https://doi.org/10.1038/ni.2555

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