Study of Comparison of Serum CXCL10 in Vitiligenous Patients before and after NB-UVB

Background Vitiligo is a common, asymptomatic, acquired depigmentation disorder, clinically characterized by milky white sharply demarcated, macules and patches that are scattered symmetrically or asymmetrically over the body causing severe cosmetic distress and social stigma. It can be classified as nonsegmental, segmental, mixed, or unclassified. In vitiligo, melanocytes are targeted by multiple aggressions leading to marked reduction and destruction of pigment cells, including autoimmune process, altered cellular environment, defective melanocytes migration, stress, and genetic factors. Objective To evaluate the serum CXCL10 level in patients with more than one year stability, compare them with healthy controls and compare the serum and tissue level before and after treatment with NB-UVB. Patients and Methods The present prospective controlled study included 20 patients with stable vitiligo (according to the VIDA activity score age of patients ranged from 18 to 54 years old were divided into 10 males and 10 females, and were recruited from the outpatient clinic of dermatology of Ain Shams University Hospital in the period from october 2018 to march 2019, twenty healthy persons were used as controls. All the patients were subjected to a full history taking, general and local clinical examination laboratory tests, and graded via VIDA score as below, digital photography were taken before and after NB-UVB. Results A Total of 20 patients were enrolled in the study, completed the study till the end of follow up of 24 visits during 12 weeks, their ages ranged from 18 to 54years old with a mean of 32.88 ± 10.42 years. Patients were divided into 10 males (50%) and 10 females (50%). Only one patient (5%) had a past medical history of diabetes mellitus and five patients (25%) had similar vitiligo affection in their families. As regard the mean difference of serum CXCL10 in comparison to tissue levels after the treatment there was no statistically significant differences indicating that serum is good indicator for measurement of expression of CXCR3 expression with less invasive procedure and tissue CXCL10 is not necessary to be measured Conclusion Cxcl10 is a useful marker for vitiligo and its severity Serum CXCL10 is equally significant to tissue CXCL10, so serum CXCL10 can replase invasive tissue CXCL10 Some drugs can be directed against CXCL10 or its receptor CXCR3 and may be a useful tool to control vitiligo in the future.

CXCR3 Expression and Genome-Wide 3′ Splice Site Selection in the TCGA Breast Cancer Cohort

CXCR3 is a chemokine receptor with two well-characterized isoforms that have unique, context-dependent roles: CXCR3-A and CXCR3-B, which are produced through alternative 3′ splice site selection (A3SS). RNA-seq data from The Cancer Genome Atlas (TCGA) were used to correlate CXCR3 expression with breast cancer progression. This analysis revealed significant CXCR3 expression patterns associated with survival and differential expression between the tumor and adjacent normal tissue. TCGA data were used to estimate abundance of immune cells in breast cancer, which demonstrated the association of CXCR3 with immune infiltration, particularly in the triple-negative subtype. Given the importance of A3SS in CXCR3, genome-wide analysis of A3SS events was performed to identify events that were differentially spliced between breast cancer tissue and adjacent normal tissue. A total of 481 splicing events in 424 genes were found to be differentially spliced. The parent genes of differentially spliced events were enriched in RNA processing and splicing functions, indicating an underappreciated role of A3SS in the integrated splicing network of breast cancer. These results further validated the role of CXCR3 in immune infiltration of tumors, while raising questions about the role of A3SS splicing.

Adaptive immunity to human coronaviruses is widespread but low in magnitude

Endemic human coronaviruses (hCoV) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T cell memory in adults. We quantified CD4 T cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2 uninfected individuals. T cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung draining lymph nodes. Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.

Human Thymic CD10+ PD-1+ Intraepithelial Lymphocyte Precursors Acquire Interleukin-15 Responsiveness at the CD1a– CD95+ CD28– CCR7– Developmental Stage

Human thymic CD8αα+ CD10+ PD-1+ αβ T cells selected through early agonist selection have been proposed as the putative thymic precursors of the human CD8αα+ intestinal intraepithelial lymphocytes (IELs). However, the progeny of these thymic precursor cells in human blood or tissues has not yet been characterized. Here, we studied the phenotypical and transcriptional differentiation of the thymic IEL precursor (IELp) lineage upon in vitro exposure to cytokines prominent in the peripheral tissues such as interleukin-15 (IL-15) and the inflammatory cytokines interleukin-12 (IL-12) and interleukin-18 (IL-18). We showed that only the CD1a− fraction of the CD10+ PD-1+ IELp population was able to proliferate with IL-15, suggesting that this subset had acquired functionality. These cells downregulated PD-1 expression and completely lost CD10 expression, whereas other surface markers such as CD95 and CXCR3 remained highly expressed. RNA-seq analysis of the IL-15-cultured cells clearly showed induction of innate-like and effector genes. Induction of the cytotoxic machinery by the CD10+ PD-1+ population was acquired in the presence of IL-15 and was further augmented by inflammatory cytokines. Our data suggest that only the CD1a− CD10+ PD-1+ population exits the thymus and survives in the periphery. Furthermore, PD-1 and CD10 expression is not an intrinsic property of this lineage, but rather characterizes a transient stage in differentiation. CD95 and CXCR3 expression combined with the absence of CD28, CCR7, and CD6 expression might be more powerful markers to define this lineage in the periphery.

High CXCR3 on Leukemic Cells Distinguishes IgHVmut from IgHVunmut in Chronic Lymphocytic Leukemia: Evidence from CD5high and CD5low Clones

Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize CD5high and CD5low neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5high and CD5low subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients (n=60) subgrouped according to the IgHV mutational status (IgHVmut, n=24; IgHVunmut, n=36). CD5high subpopulation showed a high percentage of CXCR3 (P<0.001), CCR10 (P=0.001), and CD62L (P=0.031) and high levels of CXCR5 (P=0.005), CCR7 (P=0.013) compared to CD5low cells expressing high CXCR4 (P<0.001). Comparing IgHVmut and IgHVunmut patients, high levels of CXCR3 on CD5high and CD5low subpopulations were detected in the IgHVmut patients, with better discrimination in CD5low subpopulation. Levels of CXCR3 on CD5low subpopulation were associated with time to the next treatment, thus further confirming its prognostic value. Taken together, our analysis revealed higher CXCR3 expression on both CD5high and CD5low neoplastic cells in IgHVmut with a better prognosis compared to IgHVunmut patients. Contribution of CXCR3 to CLL pathophysiology and its suitability for prognostication and therapeutic exploitation deserves future investigations.