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Members of the C-X-C motif chemokine receptor (CXCR) superfamily play central roles in initiating the innate immune response in mammalian cells by orchestrating selective cell migration and immune cell activation. With its multilayered structure, the skin, which is the largest organ in the body, performs a crucial defense function, protecting the human body from harmful environmental threats and pathogens. CXCRs contribute to primary immunological defense; these receptors are differentially expressed by different types of skin cells and act as key players in initiating downstream innate immune responses. While the initiation of inflammatory responses by CXCRs is essential for pathogen elimination and tissue healing, overactivation of these receptors can enhance T-cell-mediated autoimmune responses, resulting in excessive inflammation and the development of several skin disorders, including psoriasis, atopic dermatitis, allergic contact dermatitis, vitiligo, autoimmune diseases, and skin cancers. In summary, CXCRs serve as critical links that connect innate immunity and adaptive immunity. In this article, we present the current knowledge about the functions of CXCRs in the homeostasis function of the skin and their contributions to the pathogenesis of allergic contact dermatitis and psoriasis. Furthermore, we will examine the research progress and efficacy of therapeutic approaches that target CXCRs. [ABSTRACT FROM AUTHOR]

Members of the C-X-C motif chemokine receptor (CXCR) superfamily play central roles in initiating the innate immune response in mammalian cells by orchestrating selective cell migration and immune cell activation. With its multilayered structure, the skin, which is the largest organ in the body, performs a crucial defense function, protecting the human body from harmful environmental threats and pathogens. CXCRs contribute to primary immunological defense; these receptors are differentially expressed by different types of skin cells and act as key players in initiating downstream innate immune responses. While the initiation of inflammatory responses by CXCRs is essential for pathogen elimination and tissue healing, overactivation of these receptors can enhance T-cell-mediated autoimmune responses, resulting in excessive inflammation and the development of several skin disorders, including psoriasis, atopic dermatitis, allergic contact dermatitis, vitiligo, autoimmune diseases, and skin cancers. In summary, CXCRs serve as critical links that connect innate immunity and adaptive immunity. In this article, we present the current knowledge about the functions of CXCRs in the homeostasis function of the skin and their contributions to the pathogenesis of allergic contact dermatitis and psoriasis. Furthermore, we will examine the research progress and efficacy of therapeutic approaches that target CXCRs.

The chemokine-receptor system plays important roles in the leukocyte trafficking, inflammation, immune cell differentiation, cancer and other biological processes. In the present study, the sequence features, structures and expression patterns of twelve CXC chemokine ligands (CXCL8a.1, CXCL8a.2, CXCL8b.1, CXCL8b.2, CXCL12a, CXCL12b, CXCL13.1, CXCL13.2, CXCL14, CXCL18a, CXCL18b and CXCL19) and eight CXC chemokine receptors (CXCR1, CXCR2, CXCR3.1, CXCR3.2, CXCR3.3, CXCR4a, CXCR4b and CXCR5) of largemouth bass (Micropterus salmoides) were analyzed. All the CXCLs and CXCRs of largemouth bass shared high sequence identities with their teleost counterparts and possessed conserved motifs and structures of CXCLs and CXCRs family. Realtime qPCR revealed that these CXCLs and CXCRs were ubiquitously expressed in all examined tissues, with high expression levels in the immune-related tissues (spleen, head kidney, and gill). Following lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (polyI:C) stimulations, most of these CXCLs and CXCRs were significantly up-regulated in spleen. In addition, the potential interacted molecules of these CXCLs and CXCRs were analyzed by protein-protein interaction network analysis. To the best of our knowledge, this is the first study that in detail analyzes the CXCLs and CXCRs of largemouth bass. Our results provide valuable basis for study the function and mechanism of chemokine-receptor system in largemouth bass. • Twelve CXCLs and eight CXCRs were identified in largemouth bass. • The bioinformatics analysis of CXCLs and CXCRs were conducted. • Expressions of CXCLs and CXCRs in normal tissues of largemouth bass were analyzed. • Expressions of CXCLs and CXCRs in spleen following PAMPs stimulation were analyzed. [ABSTRACT FROM AUTHOR]

Bone marrow endothelial cells (EC) from patients with multiple myeloma (MM) were found to express and secrete higher amounts of the CXC-chemokines CXCL8/interleukin (IL)-8, CXCL11/interferon-inducible T-cell alpha chemoattractant (I-TAC), CXCL12/stromal cell-derived factor (SDF)-1α, and CCL2/monocyte chemotactic protein(MCP)-1 than EC from human umbilical vein (HUVEC), considered as a healthy counterpart. Paired plasma cells and several MM cell lines expressed cognate receptors of each chemokine to a variable extent. When cells were exposed to chemokines, CXCL8/IL-8 and CXCL12/SDF-1α stimulated their proliferation and all chemokines stimulated cell chemotaxis. It is suggested that angiogenesis also favours MM progression through the release of CXC-chemokines. [ABSTRACT FROM AUTHOR]

• Low immune lymphocyte infiltration in breast cancer. • Eight CXCRs have different roles in tumor immunity and immunotherapy. • High CXCR3/4/5/6 expressions promote immune lymphocytes infiltration in breast cancer. • High CXCR3/5/6 expression indicate better prognosis in breast cancer patients. Recently, immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma. Unfortunately, many breast cancer (BC) patients show low response to ICIs due to the lack of infiltrating immune cells. Previous studies revealed that chemokine-CXC receptors (CXCRs) play a crucial role in leukocyte infiltration and promote cancer cell proliferation, migration, metastasis, and angiogenesis. However, the underlying functions of CXCRs in cancer-immunity cycle remain unclear. In this study, we firstly found that in comparison to normal tissues, BC tissues, especially basal-like BC, showed increased mRNA levels of CXCR3/4/5/6/8, but decreased CXCR1/2/7 expression using UALCAN and TIMER database. Interestingly, it's was found that the mRNA levels of CXCR3/4/5/6 were decreased in lymphocyte depleted of the BC immune subtype. Subsequently, functional enrichment analysis of distinct CXCRs indicated that CXCR3/4/5/6 were strongly associated to immune-related biological functions. Therefore, further analysis using TIMER and TISIDB database suggested that CXCR3/4/5/6 expression were strongly correlated with tumor-infiltrating lymphocytes (TILs) and immune checkpoints in BC. Finally, Kaplan–Meier Plotter analysis indicated that high mRNA expression of CXCR4 predicted worse relapse-free survival (RFS), whereas CXCR3/5/6 indicated better RFS in BC patients. These findings suggest a therapeutic value for CXCR3/4/5/6 in combination with ICIs for the treatment of BC. [ABSTRACT FROM AUTHOR]