scholarly journals Comprehensive Analysis of the Immune Implication of TEX41 in Skin Cutaneous Melanoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhi-yong Chen ◽  
Jie-qing Huang ◽  
Yu Zhu ◽  
Yong-song Chen ◽  
Xue-feng Yu
Keyword(s):  
T Cells ◽  
Cutaneous Melanoma ◽  
Plasma Cells ◽  
Normal Skin ◽  
Comprehensive Analysis ◽  
Kegg Pathways ◽  
Enhancer Rna ◽  
Follicular Helper ◽  
Regulatory Effects

Enhancer RNAs (eRNAs), a subclass of noncoding RNAs from enhancers, have been demonstrated to exhibit important regulatory effects on the expressions of various genes. However, the role of eRNAs in skin cutaneous melanoma (SKCM) remained largely unclear. In this study, we aimed to explore the expression and prognostic value of an enhancer RNA TEX41 in SKCM as well as the associations between TEX41 and tumor-infiltrating immune cells (TICs). We observed that TEX41 expression was distinctly increased in SKCM specimens compared with normal skin specimens using GEPIA. Survival assays based on TGCA datasets revealed that patients with low TEX41 expressions displayed a longer overall survival than those with high TEX41 expression. CIBERSORT datasets revealed that TEX41 was related to 8 types of TICs (macrophages M1, T cells regulatory, plasma cells, mast cells resting, T cells CD8, dendritic cells resting, and T cells follicular helper). Three kinds of TICs were negatively related to TEX41 expressions, including macrophages M2, NK cells resting, and macrophages M0. The expressions of TEX41 were involved in five KEGG pathways, including transcriptional misregulation in cancer, SNARE interactions in vesicular transport, mitophagy-animal, melanoma, melanogenesis, and progesterone-mediated oocyte maturation. Overall, TEX41 can be used as a novel biomarker for the prognosis of SKCM patients and is associated with TICs, indicating it as a therapeutic target for SKCM.

scholarly journals Hierarchical Clustering of Cutaneous Melanoma Based on Immunogenomic Profiling

2020 ◽  
Vol 10 ◽  
Author(s):  
Jie Yu ◽  
Minyue Xie ◽  
Shengfang Ge ◽  
Peiwei Chai ◽  
Yixiong Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Cutaneous Melanoma ◽  
Plasma Cells ◽  
The Cancer Genome Atlas ◽  
Activated T Cells ◽  
Immune Signature ◽  
Follicular Helper ◽  
Gene Sets ◽  
Melanoma Prognosis ◽  
Melanoma Subtypes

Cutaneous melanoma is an aggressive malignancy with high heterogeneity. Several studies have been performed to identify cutaneous melanoma subtypes based on genomic profiling. However, few classifications based on assessments of immune-associated genes have limited clinical implications for cutaneous melanoma. Using 470 cutaneous melanoma samples from The Cancer Genome Atlas (TCGA), we calculated the enrichment levels of 29 immune-associated gene sets in each sample and hierarchically clustered them into Immunity High (Immunity_H, n=323, 68.7%), Immunity Medium (Immunity_M, n=135, 28.7%), and Immunity Low (Immunity_L, n=12, 2.6%) based on the ssGSEA score. The ESTIMATE algorithm was used to calculate stromal scores (range: -1,800.51–1,901.99), immune scores (range: -1,476.28–3,780.33), estimate scores (range: -2,618.28–5,098.14) and tumor purity (range: 0.216–0.976) and they were significantly correlated with immune subtypes (Kruskal–Wallis test, P < 0.001). The Immunity_H group tended to have higher expression levels of HLA and immune checkpoint genes (Kruskal–Wallis test, P < 0.05). The Immunity_H group had the highest level of naïve B cells, resting dendritic cells, M1 macrophages, resting NK cells, plasma cells, CD4 memory activated T cells, CD8 T cells, follicular helper T cells and regulatory T cells, and the Immunity_L group had better overall survival. The GO terms identified in the Immunity_H group were mainly immune related. In conclusion, immune signature-associated cutaneous melanoma subtypes play a role in cutaneous melanoma prognosis stratification. The construction of immune signature-associated cutaneous melanoma subtypes predicted possible patient outcomes and provided possible immunotherapy candidates.

scholarly journals An Inflammatory Loop Between Spleen-Derived Myeloid Cells and CD4+ T Cells Leads to Accumulation of Long-Lived Plasma Cells That Exacerbates Lupus Autoimmunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Eunkyeong Jang ◽  
Somi Cho ◽  
Sungjin Pyo ◽  
Jin-Wu Nam ◽  
Jeehee Youn
Keyword(s):  
T Cells ◽  
Plasma Cells ◽  
Myeloid Cells ◽  
Autoantibody Production ◽  
Clinical Phase ◽  
Follicular Helper ◽  
Inflammatory Phenotype ◽  
Cytokine Milieu

Splenic long-lived plasma cells are abnormally numerous and deleterious in systemic autoimmune diseases, yet how they accumulate remains poorly understood. We demonstrate here that a pathological role of spleen-derived CD11b+Gr-1+ myeloid cells (SDMCs) underpins the accumulation of splenic long-lived plasma cells in a lupus-prone model named sanroque. We found that SDMCs were progressively accumulated in sanroque mice from the early clinical phase. Transcriptome profiles revealed that SDMCs have a predominant shift toward an inflammatory phenotype relative to the bone marrow-derived counterparts and are distinct from neutrophils and monocytes. SDMCs were expanded in situ via splenic extramedullary myelopoiesis under the proinflammatory cytokine milieu during lupus progression. SDMCs promoted the development of IFN-γ-secreting Th1 and follicular helper T cells, thereby licensing CD4+ T cells to be pathologic activators of SDMCs and plasma cells. SDMCs also directly promoted the survival of plasma cells by providing B-cell activating factor of the TNF family. The frequency of SDMCs correlated with that of splenic long-lived plasma cells. Selective depletion of CD11b+Gr-1+ cells reduced autoantibody production in sanroque mice. Thus, our findings suggest that SDMCs expanded in situ establish a positive feedback loop with CD4+ T cells, leading to accumulation of long-lived plasma cells which exacerbates lupus autoimmunity.

scholarly journals ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity

2008 ◽  
Vol 205 (12) ◽  
pp. 2873-2886 ◽  
Author(s):  
Jared M. Odegard ◽  
Benjamin R. Marks ◽  
Leah D. DiPlacido ◽  
Amanda C. Poholek ◽  
Dwight H. Kono ◽  
...  
Keyword(s):  
T Cells ◽  
Plasma Cells ◽  
Effector T Cells ◽  
Autoantibody Production ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Systemic Autoimmunity ◽  
Helper Function ◽  
Ig G

The role of specialized follicular helper T (TFH) cells in the germinal center has become well recognized, but it is less clear how effector T cells govern the extrafollicular response, the dominant pathway of high-affinity, isotype-switched autoantibody production in the MRL/MpJ-Faslpr (MRLlpr) mouse model of lupus. MRLlpr mice lacking the Icos gene have impaired extrafollicular differentiation of immunoglobulin (Ig) G+ plasma cells accompanied by defects in CXC chemokine receptor (CXCR) 4 expression, interleukin (IL) 21 secretion, and B cell helper function in CD4 T cells. These phenotypes reflect the selective loss of a population of T cells marked by down-regulation of P-selectin glycoprotein ligand 1 (PSGL-1; also known as CD162). PSGL-1lo T cells from MRLlpr mice express CXCR4, localize to extrafollicular sites, and uniquely mediate IgG production through IL-21 and CD40L. In other autoimmune strains, PSGL-1lo T cells are also abundant but may exhibit either a follicular or extrafollicular phenotype. Our findings define an anatomically distinct extrafollicular population of cells that regulates plasma cell differentiation in chronic autoimmunity, indicating that specialized humoral effector T cells akin to TFH cells can occur outside the follicle.

scholarly journals A novel prognostic biomarker LCP2 correlates with metastatic melanoma-infiltrating CD8+ T cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zijun Wang ◽  
Mou Peng
Keyword(s):  
T Cells ◽  
Cutaneous Melanoma ◽  
Prognostic Biomarker ◽  
Normal Skin ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Tcr Signaling ◽  
Pathways Analysis ◽  
And Function

AbstractLymphocyte cytosolic protein 2 (LCP2) is one of the SLP-76 family of adapters, which are critical intermediates in signal cascades downstream of several receptors. LCP2 regulates immunoreceptor signaling (such as T-cell receptors) and is also required for integrin signaling in neutrophils and platelets. However, the role of LCP2 in the tumor microenvironment is still unknown. In this study, we found a significant increase of mRNA and protein expression of LCP2 in metastatic skin cutaneous melanoma compared to normal skin. The upregulation of LCP2 was associated with good overall survival of patients with metastatic skin cutaneous melanoma, who received pharmacotherapy and radiation. GSEA signaling pathways analysis showed that LCP2 was involved in multiple pathways of immune response and correlation analysis revealed LCP2 was positively correlated with molecules in TCR signaling and 11 immune checkpoints, while LCP2 negatively correlated with 2 immune checkpoints in the metastatic skin cutaneous melanoma. According to the different expressions of LCP2, high LCP2 expression was positively correlated with more tumor-infiltrating CD8+ T cells. Furthermore, Kaplan–Meier plot indicated that LCP2 acted as a prognostic biomarker for progression-free survival of patients with metastatic skin cutaneous melanoma receiving anti-PD1 immunotherapy. In conclusion, our results integrated both the expression and function of LCP2 in melanoma using multiple tools, shedding light on the potential role of LCP2 in melanoma, and suggesting LCP2 serves as a prognostic biomarker and therapeutic target in anti-tumor immunity.

scholarly journals Potential Role of Trace Elements (Al, Cu, Zn, and Se) in Multiple Sclerosis Physiopathology

2020 ◽  
Vol 27 (4) ◽  
pp. 163-177
Author(s):  
Mohammad Sadegh Hesamian ◽  
Nahid Eskandari
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Trace Elements ◽  
Plasma Cells ◽  
Peripheral Tolerance ◽  
The Central Nervous System ◽  
Living Organisms ◽  
Tolerance Breakdown ◽  
Peripheral Immune Cells

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system. The cause of MS is not known completely, and pathology is specified by involved demyelinated areas in the white and gray matter of the brain and spinal cord. Inflammation and peripheral tolerance breakdown due to Treg cell defects and/or effector cell resistance are present at all stages of the disease. Several invading peripheral immune cells are included in the process of the disease such as macrophages, CD8+ T cells, CD4+ T cells, B cells, and plasma cells. Trace elements are known as elements found in soil, plants, and living organisms in small quantities. Some of them (e.g., Al, Cu, Zn, Mn, and Se) are essential for the body’s functions like catalysts in enzyme systems, energy metabolism, etc. Al toxicity and Cu, Zn, and Se toxicity and deficiency can affect the immune system and following neuron inflammation and degeneration. These processes may result in MS pathology. Of course, factors such as lifestyle, environment, and industrialization can affect levels of trace elements in the human body.

scholarly journals Differential immune cell infiltrations between healthy periodontal and chronic periodontitis tissues

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei Li ◽  
Zheng Zhang ◽  
Zuo-min Wang
Keyword(s):  
T Cells ◽  
B Cells ◽  
Mast Cells ◽  
Plasma Cells ◽  
Immune Cell ◽  
Memory T Cells ◽  
Host Immunity ◽  
Memory B Cells ◽  
Helper T Cells ◽  
Follicular Helper

Abstract Background Host immunity plays an important role against oral microorganisms in periodontitis. Methods This study assessed the infiltrating immune cell subtypes in 133 healthy periodontal and 210 chronic periodontitis tissues from Gene Expression Omnibus (GEO) datasets using the CIBERSORT gene signature files. Results Plasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues, when compared to those in healthy controls. In contrast, memory B cells, resting dendritic, mast cells and CD4 memory cells, as well as activated mast cells, M1 and M2 macrophages, and follicular helper T cells, were mainly present in healthy periodontal tissues. Furthermore, these periodontitis tissues generally contained a higher proportion of activated CD4 memory T cells, while the other subtypes of T cells, including resting CD4 memory T cells, CD8 T cells, follicular helper T cells (TFH) and regulatory T cells (Tregs), were relatively lower in periodontitis tissues, when compared to healthy tissues. The ratio of dendritic and mast cells and macrophages was lower in periodontitis tissues, when compared to healthy tissues. In addition, there was a significant negative association of plasma cells with most of the other immune cells, such as plasma cells vs. memory B cells (γ = − 0.84), plasma cells vs. resting dendritic cells (γ = − 0.64), plasma cells vs. resting CD4 memory T cells (γ = 0.50), plasma cells versus activated dendritic cells (γ = − 0.46), plasma cells versus TFH (γ = − 0.46), plasma cells versus macrophage M2 cells (γ = − 0.43), or plasma cells versus macrophage M1 cells (γ = − 0.40), between healthy control and periodontitis tissues. Conclusion Plasma cells, naive B cells and neutrophils were all elevated in periodontitis tissues. The infiltration of different immune cell subtypes in the periodontitis site could lead the host immunity against periodontitis.

The potential role of follicular helper T cells and helper T cells type 1 in Warthin tumour

2021 ◽  
Vol 220 ◽  
pp. 153386
Author(s):  
Yoshiaki Kobayashi ◽  
Nozomu Kurose ◽  
Xin Guo ◽  
Akihiro Shioya ◽  
Morimasa Kitamura ◽  
...  
Keyword(s):  
T Cells ◽  
Potential Role ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Warthin Tumour ◽  
Follicular Helper
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