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

Nature Immunology volume 14, pages 446–453 (2013)Cite this article

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An Erratum to this article was published on 19 July 2013

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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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Figure 1: Lower frequency of CD4+ DCs in spleens of EBI2-deficient mice.
Figure 2: EBI2 expression on splenic DCs.
Figure 3: EBI2 mediates the migration of CD4+ DCs toward 7α,25-OHC and the localization of DCs to splenic bridging channels.
Figure 4: Production of 7α,25-OHC is required for the development of CD4+ DCs and localization of DCs in marginal zone bridging channels.
Figure 5: Normal development of splenic CD4+ DCs depends on intrinsic expression of EBI2.
Figure 6: EBI2 is not required for normal development of DC precursors or survival of splenic DCs.
Figure 7: EBI2 expression on DCs is required for normal induction of B cell and T cell responses.

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  • 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.)

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Authors and 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.

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Correspondence to Dominique Gatto or Robert Brink.

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Gatto, D., Wood, K., Caminschi, I. et al. The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat Immunol 14, 446–453 (2013). https://doi.org/10.1038/ni.2555

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