CXCR5
C-X-C chemokine receptor type 5 (CXC-R5) (CXCR-5) (Burkitt lymphoma receptor 1) (Monocyte-derived receptor 15) (MDR-15) (CD185 antigen) [BLR1] [MDR15]
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The CXCR5 (C-X-C motif chemokine receptor 5) is chemokine transmembrane receptor, acting via its ligand CXCL13 and plays a crucial role in controlling the trafficking of inflammatory cells into and from the sub-retinal space, which contributes to the pathogenesis of AMD. We have previously described the genetic ablation of CXCR5 deficiency causes RPE/choroid abnormalities and retinal degeneration (RD) in aged mice. Here we report the transcriptome data (RNA-Seq) of 24 months old CXCR5 knockout (KO) and age-matched C57BL/6 controls (WT). RNA sequencing was performed on the Illumina HiSeq 2500, providing up to 300 GB of sequence information per flow cell. The quality of RNA-seq libraries, RNA intensity were validated by Agilent Technologies Bioanalyzer-2100. The raw datasets contains on average 292,004,59 reads (after trimming 284,862,43 reads) in retina and 272,527,90 reads (after trimming 266,173,11 reads) in choroid samples. The mapped reads showed that a total of 1586 genes in retina and 1462 genes in choroid are differentially expressed in this experiment. The raw datasets were deposited into NCBI Sequence Read Archive (SRA) database and can be accessed via accession number PRJNA588421.
Keywords
- CXCR5
- FastQC
- RNA-Seq
- aging
- choroid
- mice
- retina
- retinal degeneration
Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19 CD45R CD21 CD23 ) and a decrease of naive B cells (CD19 IgD ), whereas there is an enhancement of a CD19 CD45R innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R CD21 CD23 CD5 CD11b ) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice. These changes in aged SAMP8 mice were associated with lower IgG isotype levels, displaying low variable gene usage repertoires of the immunoglobulin heavy chain (V ) diversity, with a diminution on IgG1-memory B cells (CD11b Gr1 CD138 IgM IgD CD19 CD38 IgG1 ), an increase in T follicular helper (T , CD4 CXCR5 PD1 ) cell numbers, and an altered MOMA-1 (metallophilic macrophages) band in primary follicles. LPS-mediated IgG1 responses were impaired in the B1REL and ABC cell compartments, both in vitro and in vivo. These data demonstrate the prominent changes to different B cell populations and in structural follicle organization that occur upon aging in SAMP8 mice. These novel results raise new questions regarding the importance of the cellular distribution in the B cell layers, and their effector functions needed to mount a coordinated and effective humoral response.
MeSH Terms
- Aging
- Animals
- Antigens, CD
- B-Lymphocytes
- Cell Death
- Cell Proliferation
- Gene Expression Regulation, Developmental
- IgG Deficiency
- Immunity, Humoral
- Immunity, Innate
- Immunoglobulin D
- Immunoglobulin G
- Immunoglobulin Heavy Chains
- Immunoglobulin M
- Immunologic Memory
- Lipopolysaccharides
- Mice, Inbred C57BL
- Mice, Transgenic
- Primary Cell Culture
- Signal Transduction
- Spleen
- T-Lymphocytes, Helper-Inducer
The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25 CD127 and also FOXP3 CXCR5 cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4 CXCR3 (Th2 and Th17), CTLA4 and FOXP3 subsets were present in significantly higher frequencies, whereas CCR4 (Th1/Th17, CCR6 CCR4 CXCR3 , and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3 /interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4 CXCR3 T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.
MeSH Terms
- Adult
- Aged
- Aging
- Antigens, Differentiation, T-Lymphocyte
- Arthritis, Rheumatoid
- Case-Control Studies
- Cytokines
- Disease Progression
- Female
- Flow Cytometry
- Gene Expression Profiling
- Humans
- Immunophenotyping
- Lymphocyte Count
- Male
- Middle Aged
- Receptors, CXCR3
- T-Lymphocyte Subsets
- T-Lymphocytes, Helper-Inducer
- T-Lymphocytes, Regulatory
- Transcription Factors
Keywords
- T cell profile
- autoimmunity
- chemokine receptors
- multivariate discriminant analysis
The impairment of humoral immune response in elderly humans has been extensively demonstrated. We have reported the increase of memory B cells (IgG( )IgD(-)CD27(-), double negative, DN) population in the elderly, in which there is also a typical inflammatory micro-environment. In order to evaluate whether this pro-inflammatory status could influence the trafficking phenotype of naïve/memory B cells, we have assessed the expression of CCR7, CCR6, CXCR3, CXCR4, CXCR5 and CD62L on naïve/memory B cell subpopulations in young and elderly subjects. Moreover, the combination of pro-inflammatory interleukin-21 (IL-21) and B cell receptor (BCR) stimulation enables B cells to produce and secrete granzyme B (GrB), which plays a critical role in early anti-viral immune responses, in the regulation of autoimmune mechanisms and in cancer immunosurveillance. Our data demonstrate that in the elderly, naïve/memory B cell populations present a different expression of the studied receptors that could be discussed in terms of "inflamm-aging". In particular IgG( )IgD(-)CD27(-) DN B cells show a tissue trafficking phenotype and they can be stimulated to produce GrB.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- B-Lymphocyte Subsets
- Granzymes
- Humans
- Immunoglobulin D
- Immunoglobulin G
- Interleukins
- L-Selectin
- Phenotype
- Receptors, CXCR
- Tumor Necrosis Factor Receptor Superfamily, Member 7
Keywords
- B lymphocytes
- Chemokine receptors
- Elderly
- Granzyme B
- IL-21
- Inflamm-aging