CCR9
C-C chemokine receptor type 9 (C-C CKR-9) (CC-CKR-9) (CCR-9) (G-protein coupled receptor 28) (GPR-9-6) (CDw199 antigen) [GPR28]
Publications[править]
Aging results in attenuation of abilities to mount appropriate immune responses. The influence of aging on CD4( ) T cell migration ability toward chemokines was investigated with young and aged mice. We found functional decline in migration ability toward CCL19 and also decreased CCR7 expression level in antigen-stimulated CD4( ) T cells from aged mice compared with those from young mice. Upon addition of retinoic acid (RA), CD4( ) T cells from aged mice showed decreased CCR9 expression level compared to young mice and the migration ability of CD4( ) T cells from aged mice toward CCL25 was attenuated compared to young mice. We also observed that the expression of RALDH2 mRNA was decreased in mesenteric lymph node dendritic cells from aged mice compared to those from young mice. These results demonstrate that attenuated migration abilities of CD4( ) T cells were observed in aged mice, which correlated with decreased chemokine receptor expression. Furthermore, the reduced production and response to RA by aging may be one of the causes of such attenuated migration abilities in the intestinal immune system.
MeSH Terms
- Aging
- Aldehyde Dehydrogenase 1 Family
- Aldehyde Oxidoreductases
- Animals
- CD4-Positive T-Lymphocytes
- Cell Movement
- Chemokine CCL19
- Chemokines, CC
- Female
- Gene Expression Regulation, Enzymologic
- Integrins
- Isoenzymes
- Mice
- RNA, Messenger
- Receptors, CCR
- Receptors, CCR7
- Receptors, Chemokine
- Retinal Dehydrogenase
- Spleen
- Tretinoin
Keywords
- T cell
- aging
- migration
CCR9 mediates chemotaxis in response to CCL25/thymus-expressed chemokine and is selectively expressed on T cells in the thymus and small intestine. To investigate the role of CCR9 in T cell development, the CCR9 gene was disrupted by homologous recombination. B cell development, thymic alphabeta-T cell development, and thymocyte selection appeared unimpaired in adult CCR9-deficient (CCR9(-/-)) mice. However, competitive transplantation experiments revealed that bone marrow from CCR9(-/-) mice was less efficient at repopulating the thymus of lethally irradiated Rag-1(-/-) mice than bone marrow from littermate CCR9( / ) mice. CCR9(-/-) mice had increased numbers of peripheral gammadelta-T cells but reduced numbers of gammadeltaTCR( ) and CD8alphabeta( )alphabetaTCR( ) intraepithelial lymphocytes in the small intestine. Thus, CCR9 plays an important, although not indispensable, role in regulating the development and/or migration of both alphabeta(-) and gammadelta(-) T lymphocytes.
MeSH Terms
- Aging
- Animals
- B-Lymphocyte Subsets
- Bone Marrow Cells
- Cell Differentiation
- Cells, Cultured
- Chemotaxis, Leukocyte
- Crosses, Genetic
- Hematopoiesis
- Intestinal Mucosa
- Lymph Nodes
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Organ Specificity
- Receptors, Antigen, T-Cell, alpha-beta
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, CCR
- Receptors, Chemokine
- Spleen
- T-Lymphocyte Subsets
- Thymus Gland
The chemokine receptor CCR9 is reported to be predominantly expressed by thymocytes as well as by circulating gut-homing and resident T cells in the small intestinal mucosa. Its ligand thymus-expressed chemokine (TECK) is produced by thymic and small intestinal epithelium. Here we report that the proportion of circulating CCR9 naive T cells (mostly CD4 ) declines with age, from approximately 15% of all T cells at birth to around 1% in adults. The proportion of CCR9 T cells lacking the classical gut-homing receptor alpha4beta7, was much higher in children than in adults. Therefore, circulating CD3 CCR9 CD45RA cells have most likely left the thymus quite recently. This notion was supported by the small number of CCR9 naive T cells which was present shortly after thymectomy. Establishing a phenotypic marker for recent thymic emigrants might provide a powerful tool in the clinical assessment and follow-up after cancer chemotherapy, hematopoietic stem cell transplantation, and during antiretroviral treatment of human immunodeficiency virus (HIV)-infected patients.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- CD3 Complex
- CD4-Positive T-Lymphocytes
- Cell Movement
- Child
- Child, Preschool
- Flow Cytometry
- Humans
- Infant
- Infant, Newborn
- Leukocyte Common Antigens
- Middle Aged
- Receptors, CCR
- Receptors, Chemokine
- T-Lymphocyte Subsets
- Thymectomy
- Thymus Gland
Chemokines appear to have an important role in the seeding of lymphoid progenitors in the thymus, the regulation of the coordinated movements of the maturing T cells within this organ, and the egress of the resulting naive T cells to secondary lymphoid organs. CCR9, the specific receptor for the beta-chemokine TECK/CCL25, is selectively expressed in thymus, lymph node, and spleen. Using a specific anti-CCR9 polyclonal antibody, K629, and a semiquantitative reverse transcriptase-polymerase chain reaction procedure, a detailed study of CCR9 expression in the thymus and secondary lymphoid organs was performed. The results show that CD4( )CD8( ) double-positive thymocytes have the highest CCR9 expression in thymus. Single-positive CD8( ) thymocytes continue to express this receptor after abandoning the thymus as mature naive T cells, as suggested by the existence of a CD8( )CD69(low)CD62L(high) CCR9( ) cell subset. Consistent with this, CD8( ) lymphocytes from lymph nodes, spleen, and Peyer patches express a functional CCR9, as its expression correlates with migration in response to CCL25. Conversely, CD4( ) thymocytes lose CCR9 before abandoning the thymus, and CD4( ) T cells from secondary lymphoid organs also lack CCR9 expression. Analysis of CCR9 expression in thymocytes from mice of different ages showed that CCR9 levels are affected by age, as this receptor is more abundant, and its response to CCL25 is more potent in newborn animals. Collectively, these results suggest that CCR9 has a role in thymocyte development throughout murine life, with clear differences between the CD4( ) and CD8( ) lineages.
MeSH Terms
- Aging
- Animals
- CD4-Positive T-Lymphocytes
- CD8-Positive T-Lymphocytes
- Cell Differentiation
- Cell Lineage
- Chemokines, CC
- Chemotaxis
- DNA-Binding Proteins
- Gene Expression Profiling
- Lymph Nodes
- Lymphoid Tissue
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Muromonab-CD3
- Peyer's Patches
- RNA, Messenger
- Rabbits
- Receptors, CCR
- Receptors, Chemokine
- Recombinant Fusion Proteins
- Reverse Transcriptase Polymerase Chain Reaction
- Spleen
- T-Lymphocyte Subsets
- Thymus Gland
- Transfection