Last update 01 Nov 2024

CD4 x SORT1

Last update 01 Nov 2024

Basic Info

Related Targets

CD4SORT1

Drugs associated with CD4 x SORT1

VGD071

Target

CD4 x SORT1

Mechanism

CD4 inhibitors [+1]

Active Org.

University of Gothenburg

Originator Org.

University of Gothenburg

Active Indication

Breast Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CD4 x SORT1

100 Translational Medicine associated with CD4 x SORT1

0 Patents (Medical) associated with CD4 x SORT1

Literatures (Medical) associated with CD4 x SORT1

15 Jan 2024·The FASEB Journal

Upregulation of proBDNF/p75NTR signaling in immune cells and its correlation with inflammatory markers in patients with major depression

Article

Author: Yang, Chun-Rui ; Zhou, Fiona ; Wang, Zhi-Qiang ; Zhang, Xiao-Yang ; Zhou, Xin-Fu ; Meng, Fan-Jie ; Liu, Shuang ; Liang, Rui ; Liu, Yuan ; Ning, Li

AbstractProBDNF is the precursor protein of brain‐derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and p75 neurotrophic receptors (p75NTR) in major depressive disorder (MDD) were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n = 32) and normal donors (n = 20). We examined the expression of proBDNF and inflammatory markers and their correlative relationship in patients with major depression. Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Finally, the role of proBDNF/p75NTR signal in inflammatory immune activity of PBMCs was verified in vitro experiments. Inflammatory cytokines in PBMC from MDD patients were increased and correlated with the major depression scores. The levels of IL‐1β and IL‐10 were also positively correlated with the major depression scores, while the levels of TNF‐α and IL‐6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin were positively correlated with IL‐1β. Q‐PCR and Western blots showed proBDNF, p75NTR, and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T cells. The number of proBDNF and p75NTR positive CD4+ and CD8+ T cells from MDD patients was increased and subsequently reversed after therapeutic management. Exogenous proBDNF protein or p75ECD‐Fc treatment of cultured PBMC affected the release of inflammatory cytokines in vitro. ProBDNF promoted the expression of inflammatory cytokines, while p75ECD‐Fc inhibited the expression of inflammatory cytokines. Given there was an inflammatory response of lymphocytes to proBDNF, it is suggested that proBDNF/p75NTR signaling may upstream inflammatory cytokines in MDD. Our data suggest that proBDNF/p75NTR signaling may not only serve as biomarkers but also may be a potential therapeutic target for MDD.

01 Mar 2022·The FASEB JournalQ2 · BIOLOGY

proBDNF/p75NTR promotes rheumatoid arthritis and inflammatory response by activating proinflammatory cytokines

Q2 · BIOLOGY

Article

Author: Li, De‐Dong ; Han, Chen‐Yang ; Zhang, Xiao‐Yang ; Wang, Shuo ; Zhang, Xiang‐Lian ; Yang, Chun‐Rui ; Meng, Fan‐Jie ; Zhou, Fiona‐H. ; Yu, Miao ; Sun, Wei‐Zong ; Ding, Hong‐Jun ; Zhou, Xin‐Fu ; Meng, Bin ; Liang, Rui

P75 pan-neurotrophin receptor (p75NTR) is an important receptor for the role of neurotrophins in survival and death of neurons during development and after nerve injury. Our previous research found that the precursor of brain-derived neurotrophic factor (proBDNF) regulates pain as an inflammatory mediator. The current understanding of the role of proBDNF/p75NTR signaling pathway in inflammatory arthritis pain and rheumatoid arthritis (RA) is unclear. We recruited 20 RA patients, 20 healthy donors (HDs), and 10 osteoarthritis (OA) patients. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of proBDNF and p75NTR in synovial membrane were performed and evaluated. We next examined the mRNA and protein expression of proBDNF/p75NTR signaling pathway in peripheral blood mononuclear cells (PBMCs) and synovial tissue. ELISA and flow cytometry were assessed between the blood of RA patients and HD. To induce RA, collagen-induced arthritis (CIA) were induced in mice. We found over-synovitis of RA synovial membrane compared to OA controls in histologic sections. P75NTR and sortilin mRNA, and proBDNF protein level were significantly increased in PBMCs of RA patients compared with the HD. Consistently, ELISA showed that p75NTR, sortilin, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels in the serum of RA patients were increased compared with HD and p75NTR, sortilin were positively correlated with Disease Activity Score in 28 joints (DAS28). In addition, using flow cytometry we showed that the increased levels of proBDNF and p75NTR characterized in CD4⁺ and CD8⁺ T cells of RA patients were subsequently reversed with methotrexate (MTX) treatment. Furthermore, we found pathological changes, inflammatory pain, upregulation of the mRNA and protein expression of proBDNF/p75NTR signaling pathway, and upregulation of inflammatory cytokines in spinal cord using a well-established CIA mouse model. We showed intravenous treatment of recombinant p75ECD-Fc that biologically blocked all inflammatory responses and relieved inflammatory pain of animals with CIA. Our findings showed the involvement of proBDNF/p75NTR pathway in the RA inflammatory response and how blocking it with p75ECD-Fc may be a promising therapeutic treatment for RA.

01 Feb 2022·Annals of Translational MedicineQ4 · MEDICINE

Establishment and validation of a novel immune-related prognostic signature in malignant pleural mesothelioma

Q4 · MEDICINE

Article

Author: Zhang, Kejian ; Wang, Zhexin ; Zhang, Xiangxin ; Huang, Xiangdong

BackgroundImmune-related genes (IRGs) play an important role in the tumor immune microenvironment and affect tumor prognosis. This study aimed to establish a prognostic signature for malignant pleural mesothelioma (MPM) patients.MethodsWe obtained the relevant data of MPM patients in The Cancer Genome Atlas (TCGA), and univariate and multivariate Cox regression were used to construct the prediction signature and verify it with the external validation dataset GSE2549. A nomogram was then constructed, and its predictive ability was evaluated and analyzed the level of immune cell infiltration in different groups in the signature.ResultsAn IRG-related prognostic signature composed of INHBA, CAT, SORT1, TNFSF13B, and BIRC5 was constructed, with patients divided into high-risk and low-risk groups according to the risk score. The survival time of overall survival (OS), progression-free survival (PFS), disease-free interval (DFI), and relapse-free survival (RFS) in low-risk groups was longer than in high-risk groups. Furthermore, the signature had high predictive performance, and the receiver operating characteristic (ROC) of 1, 2, and 3 years could reach 0.853, 0.881, and 0.914, respectively. The predictive accuracy of the signature was verified by using the independent GSE2549 dataset. The levels of activated CD4 T cells, immature dendritic cells, and type 2 T helper cells were higher in high-risk patients. The gene set enrichment analysis (GSEA) analysis showed that a high concentration and P53 signal pathways were found in high-risk groups.ConclusionsThis research developed and verified a new type of immune prognostic signature based on five IRGs, which can predict the prognosis of tumor patients and provide new ideas for individualized treatment.

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