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An Indispensable Role for the Chemokine Receptor CCR10 in IgA Antibody-Secreting Cell Accumulation¹

Olivier Morteau^2,*, Craig Gerard^*, Bao Lu^*, Sorina Ghiran^*, Miriam Rits^*, Yuko Fujiwara, Yuetching Law, Kathryn Distelhorst, Elizabeth M. Nielsen, Erica D. Hill, Raymond Kwan, Nicole H. Lazarus, Eugene C. Butcher and Eric Wilson^3,

^* Perlmutter Laboratory and Department of Pediatrics and Division of Hematology and Oncology, Children’s Hospital, Harvard Medical School, Boston, MA 02115; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602; and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305

The differential expression of chemokines and chemokine receptors, by tissues and leukocytes, respectively, contributes to the specific accumulation of leukocyte subsets to different tissues. CCR10/CCL28 interactions are thought to contribute to the accumulation of IgA Ab-secreting cells (ASC) to mucosal surfaces, such as the gastrointestinal tract and the lactating mammary gland. Although the role of CCL28 in lymphocyte homing is well established, direct in vivo evidence for CCR10 involvement in this process has not been previously shown. In this study, we describe the generation of a CCR10-deficient mouse model. Using this model, we demonstrate that CCR10 is critical for efficient localization and accumulation of IgA ASC to the lactating mammary gland. Surprisingly, IgA ASC accumulation to the gastrointestinal tract is minimally impacted in CCR10-deficient mice. These results provide the first direct evidence of CCR10 involvement in lymphocyte homing and accumulation in vivo, and demonstrate that reliance on CCR10-mediated recruitment of IgA ASC varies dramatically within mucosal tissues.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants RAI072769A (to E.W.), GM37734 and AI19957 (to E.C.B.), and AI39759 (to C.G.).

² Current address: MediGene, 57c Milton Park, Abingdon, OX14 4RX, U.K.

³ Address correspondence and reprint requests to Dr. Eric Wilson, Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602. E-mail address: ericwilson{at}byu.edu. Requests for CCR10^–/– mice should be directed to Dr. Craig Gerard, Perlmutter Laboratory and Department of Pediatrics, Children’s Hospital, Harvard Medical School, Boston, MA 02115. E-mail address: craig.gerard{at}childrens.harvard.edu

⁴ Abbreviations used in this paper: ASC, Ab-secreting cell; EGFP, enhanced GFP; ES, embryonic stem; RT, room temperature.