Chemokine receptor CCR9 contributes to the localization of plasma cells to the small intestine
JOURNAL OF EXPERIMENTAL MEDICINE
Authors: Pabst, O; Ohl, L; Wendland, M; Wurbel, MA; Kremmer, E; Malissen, B; Forster, R
Abstract
Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA(+) PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA(+) PCs express high levels of CCK9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA(+) PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR-9-deficient IgA(+) PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.
CCR9 in cancer: oncogenic role and therapeutic targeting
JOURNAL OF HEMATOLOGY & ONCOLOGY
Authors: Tu, Zhenbo; Xiao, Ruijing; Xiong, Jie; Tembo, Kingsley M.; Deng, Xinzhou; Xiong, Meng; Liu, Pan; Wang, Meng; Zhang, Qiuping
Abstract
Cancer is currently one of the leading causes of death worldwide and is one of the most challenging major public health problems. The main challenges faced by clinicians in the management and treatment of cancer mainly arise from difficulties in early diagnosis and the emergence of tumor chemoresistance and metastasis. The structures of chemokine receptor 9 (CCR9) and its specific ligand chemokine ligand 25 (CCL25) have been elucidated, and, interestingly, a number of studies have demonstrated that CCR9 is a potential tumor biomarker in diagnosis and therapy, as it has been found to be highly expressed in a wide range of cancers. This expression pattern suggests that CCR9 may participate in many important biological activities involved in cancer progression. Researchers have shown that CCR9 that has been activated by its specific ligand CCL25 can interact with many signaling pathways, especially those involved in tumor chemoresistance and metastasis. This review, therefore, focuses on CCR9 induction activity and summarizes what is currently known regarding its role in cancers and its potential application in tumor-targeted therapy.