ABSTRACT
Epithelial tissues covering the external and internal surface of a body are constantly under physical, chemical or biological assaults. To protect the epithelial tissues and maintain their homeostasis, multiple layers of immune defense mechanisms are required. Besides the epithelial tissue-resident immune cells that provide the first line of defense, circulating immune cells are also recruited into the local tissues in response to challenges. Chemokines and chemokine receptors regulate tissue-specific migration, maintenance and functions of immune cells. Among them, chemokine receptor CCR10 and its ligands chemokines CCL27 and CCL28 are uniquely involved in the epithelial immunity. CCL27 is expressed predominantly in the skin by keratinocytes while CCL28 is expressed by epithelial cells of various mucosal tissues. CCR10 is expressed by various subsets of innate-like T cells that are programmed to localize to the skin during their developmental processes in the thymus. Circulating T cells might be imprinted by skin-associated antigen- presenting cells to express CCR10 for their recruitment to the skin during the local immune response. On the other hand, IgA antibody-producing B cells generated in mucosa-associated lymphoid tissues express CCR10 for their migration and maintenance at mucosal sites. Increasing evidence also found that CCR10/ligands are involved in regulation of other immune cells in epithelial immunity and are frequently exploited by epithelium-localizing or -originated cancer cells for their survival, proliferation and evasion from immune surveillance. Herein, we review current knowledge on roles of CCR10/ligands in regulation of epithelial immunity and diseases and speculate on related important questions worth further investigation.
Subject(s)
Humans , B-Lymphocytes , Cell Biology , Allergy and Immunology , Cell Lineage , Cell Movement , Genetics , Allergy and Immunology , Chemokine CCL27 , Genetics , Allergy and Immunology , Chemokines, CC , Genetics , Allergy and Immunology , Epithelial Cells , Cell Biology , Allergy and Immunology , Epithelium , Allergy and Immunology , Gene Expression Regulation , Allergy and Immunology , Immunity, Mucosal , Immunoglobulin A , Allergy and Immunology , Mucous Membrane , Cell Biology , Allergy and Immunology , Receptors, CCR10 , Genetics , Allergy and Immunology , Signal Transduction , Genetics , Allergy and Immunology , T-Lymphocytes , Cell Biology , Allergy and ImmunologyABSTRACT
Objective: To study the anti-tumor efficacy induced by antibodized tumor epitope PDTRP gene immunization. Methods: Three copies of tumor associate gene PDTRP from MUCI tandem repeats were designed and mimicked the conformation of MUCI by Insight Ⅱ . The ?lneo-PDTRP plasmid was further constructed, in which the PDTRP target gene was inserted into CDR3 of the ?1 -neo vector. The specific humoral and cellular immune responses towards to PDTRP were detected after intraspleen immunized Balb/c mice with "ylneo-PDTRP. And the immune protection assay was also done to observe whether the mice immunized with ?lneo-PDTRP could prolong the survival after tumor challenge. Results: The conformation of three copies of PDTRP mimicked the conformation of MUCI tandem repeats. The expression of ?lneo-PDTRP could be detected after in vitro transfect. The specific antibody against PDTRP epitope could be induced and increase to a higher titer after intraspleen injection with a ?lneo-PDTRP plasmid. And the specific proliferation and cytotox-ic function of lymphocyte were also increased. There is a significant survival from mice immunized with ?lneo-PDTRP a-gainst the 4T1-PDTRP tumor challenge. Conclusions: Gene immunization with ?lneo-PDTRP could elicit both humoral and cellular tumor specific immune response and had the protective effect.