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An indispensable role for the chemokine receptor CCR10 in IgA antibody-secreting cell accumulation
Authors:Morteau Olivier  Gerard Craig  Lu Bao  Ghiran Sorina  Rits Miriam  Fujiwara Yuko  Law Yuetching  Distelhorst Kathryn  Nielsen Elizabeth M  Hill Erica D  Kwan Raymond  Lazarus Nicole H  Butcher Eugene C  Wilson Eric
Affiliation:Perlmutter Laboratory and Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
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.
Keywords:
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