Last update 01 Nov 2024

IL-7Rα x Tubulin

Last update 01 Nov 2024

Basic Info

Related Targets

IL-7RαTubulin

Drugs associated with IL-7Rα x Tubulin

IL-7R-targeting antibody-drug conjugates(National Cancer Center/RIKEN)

Target

IL-7Rα x Tubulin

Mechanism

IL-7Rα inhibitors [+1]

Active Org.

Japanese National Cancer Center [+1]

Originator Org.

Riken Corp.

Active Indication

Autoimmune Diseases [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IL-7Rα x Tubulin

100 Translational Medicine associated with IL-7Rα x Tubulin

0 Patents (Medical) associated with IL-7Rα x Tubulin

Literatures (Medical) associated with IL-7Rα x Tubulin

01 Oct 2024·International Immunopharmacology

The effects of immunomodulatory drugs on cerebral small vessel disease: A mediation Mendelian randomization analysis

Article

Author: Lv, Yanchen

BACKGROUNDThere are only a few recognized drug targets for cerebral small vessel disease (CSVD). Though inflammation is increasingly implicated in the development of CSVD, it remains unclear whether immunomodulation could become a therapeutic target. Accordingly, the Mendelian randomization (MR) method was used to assess the genetically proxied impacts of IL6 receptor (IL6R) inhibitor, IL1β inhibitor, Tumor necrosis factor (TNF) inhibitor and β-tubulin inhibitor on CSVD through.METHODSSingle nucleotide polymorphisms (SNPs) near the IL6R, IL1β, TNFRSF1A and β-tubulin genes were identified as genetic proxies for immunomodulatory drugs. These SNPs exhibited significant associations with serum C-reactive protein (CRP) levels in a large European genome-wide association study. The causal effects of immunomodulatory drugs on CSVD manifestations and the mediation influence of 731 peripheral blood immune phenotypes linking these drugs to CSVD manifestations were examined using a two-sample two-step MR approach.RESULTSA total of 9, 18, 4 and 1 SNP were identified to proxy the effects of IL1β inhibitor, IL6R inhibitor, TNF inhibitor and β-tubulin inhibitor, respectively. MR analysis showed a significant causal relationship between IL1β inhibition and reduced volume of periventricular white matter hyperintensity (PWMH). IL6R inhibition was associated with a reduced risk of small vessel stroke, decreased axial diffusivity and mean diffusivity. Genetically proxied TNF inhibition may decrease the occurrence of cerebral microbleeds (CMBs) and severe enlarged perivascular spaces located at white matter (WM-EPVS). It could also protect WM integrity, as evidenced by the reduced volumes of PWMH and deep white matter hyperintensity (DWMH). Various peripheral blood immune phenotypes exhibited significant associations with immunomodulatory drugs. Notably, the median fluorescence intensity (MFI) of CD45 on CD8^br cells partially mediated the effects of IL1β inhibitor on PWMH volume. Indirect effects of TNF inhibition on PWMH and DWMH volume through the MFI of CD127 on CD28- CD8^br cells were observed. The effects of TNF inhibition on the occurrence of any CMBs were partially mediated by the MFI of CD45 on natural killer T cells, and the effects of TNF inhibition on the occurrence of lobar CMBs were partially mediated by the MFI of HLA DR on CD33- HLA DR+ cells. Furthermore, the MFI of HLA DR on CD33- HLA DR+ cells partially mediated the effects of TNF inhibition on WM-EPVS.CONCLUSIONSIL1β inhibitor, IL6R inhibitor and TNF inhibitor were associated with lower burden of CSVD while the activation of certain immune cells such as Tregs and myeloid cells partially mediated their protective effects.

01 Oct 1997·Journal of immunology (Baltimore, Md. : 1950)

Gamma delta T cells of human early pregnancy decidua: evidence for local proliferation, phenotypic heterogeneity, and extrathymic differentiation.

Article

Author: Nagaeva, O ; Hammarström, M L ; Hammarström, S ; Sundqvist, K G ; Kling, M ; Baranov, V ; Mincheva-Nilsson, L

The uterine mucosa in pregnancy, the decidua, allows placenta formation and survival of the fetus despite the fact that it is semiallogeneic. Decidua contains large numbers of lymphocytes, of which CD56+ cells dominate, followed by T cells expressing either alpha beta or gamma delta TCR. We have investigated the developmental relationship between the CD56- and TCR gamma delta-expressing cells in early pregnancy decidua using dual labeling immunoelectron microscopy, immunoflow cytometry, and cell fractionation. Lymphocyte subpopulations were, in addition, analyzed for expression of the cytokine receptor for IL-7 and c-kit and for mRNA expression of recombinase-activating genes 1 and 2. Four different cell populations could be distinguished: CD56+bright, CD56+dim/TCR gamma delta+low, CD56+dim/TCR gamma delta+high, and TCR gamma delta+low. Recombinase-activating genes 1 and 2 were expressed in the CD56+bright cells and to a limited degree in CD56+dim/TCR gamma delta+low cells. c-kit was preferentially expressed on the CD56+bright cells, while IL-7R was preferentially expressed on CD56+dim/TCR gamma delta+low and CD56+dim/TCR gamma delta+high cells. The CD56+dim TCR gamma delta+low and CD56+dim/TCR gamma delta+high cells displayed the characteristic morphology of large granular lymphocytes, while single positive TCR gamma delta+low cells were usually smaller and did not contain cytoplasmic granules. The gamma delta 1 gene segment was almost exclusively used in the TCR. Gamma delta T cells in mitosis were seen. We suggest that human early pregnancy decidua is a transient site for extrathymic maturation and that the progenitors of TCR gamma delta+ cells are bone marrow-derived immature cells expressing the CD56 (neural cell adhesion molecule) homing receptor.

PLOS ONEQ3 · CROSS-FIELD

Bariatric Surgery Induces Disruption in Inflammatory Signaling Pathways Mediated by Immune Cells in Adipose Tissue: A RNA-Seq Study

Q3 · CROSS-FIELD

ArticleOA

Author: Bouillot, Jean-Luc ; Pelloux, Véronique ; Poitou, Christine ; Chelghoum, Nadjim ; Torcivia, Adriana ; Tiret, Laurence ; Durand, Hervé ; Aron-Wisnewsky, Judith ; Mathieu, François ; Alili, Rohia ; Parks, Brian W ; Blum, Yuna ; Truong, Vinh ; Clément, Karine ; Ninio, Ewa ; Perret, Claire

BACKGROUNDBariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood.METHODOLOGY/PRINCIPAL FINDINGSWe analyzed RNA-seq expression profiles in adipose tissue from 22 obese women before and 3 months after surgery. Of 15,972 detected genes, 1214 were differentially expressed after surgery at a 5% false discovery rate. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, 26 modules of coexpressed genes were identified. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue. A first module reflecting a non-specific signature of innate immune cells, mainly macrophages, was highly conserved after surgery with the exception of DUSP2 and CD300C. A second module reflected the adaptive immune response elicited by T lymphocytes; after surgery, a disconnection was observed between genes involved in T-cell signaling and mediators of the signal transduction such as CXCR1, CXCR2, GPR97, CCR7 and IL7R. A third module reflected neutrophil-mediated inflammation; after surgery, several genes were dissociated from the module, including S100A8, S100A12, CD300E, VNN2, TUBB1 and FAM65B. We also identified a dense network of 19 genes involved in the interferon-signaling pathway which was strongly preserved after surgery, with the exception of DDX60, an antiviral factor involved in RIG-I-mediated interferon signaling. A similar loss of connection was observed in lean mice compared to their obese counterparts.CONCLUSIONS/SIGNIFICANCEThese results suggest that improvements of the inflammatory state following surgery might be explained by a disruption of immuno-inflammatory cascades involving a few crucial molecules which could serve as potential therapeutic targets.

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