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MAPK signaling in spermatogenesis and male infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Archana Devi, Bhavana Kushwaha, Gopal Gupta
It is well established that p38 regulates cell adhesion and motility by tempering actin organization via an actin-polymerizing factor, HSP27, or by changing the transcriptional expression of various adhesion molecules. All isoforms of p38 MAPK except p38-γ are found in the testes (13). TGF-β3 is involved in the activation of the p38 MAPK cascade, and when added to Sertoli cell cultures in vitro, it leads to the disruption of Sertoli cell TJ-barrier that can partially be reversed by a p38-specific inhibitor, SB202190 (47). It has been reported that epithelial TGF-β3 levels are increased during the cadmium-driven BTB restructuring, resulting in the BTB disassembly, which is accompanied by apical ES disintegration. The effect of this cytokine is partly mediated by the p38 MAPK, since an intratesticular injection of SB202190 before the cadmium application blocks the cadmium-mediated disruption of junction-associated proteins in the testes as well as impedes the expression of proteases at the cellular interface (48). Also, the inhibition of the p38 MAPK pathway averts the disruption of TJ-associated junction components, occludin and ZO-1, and apical ES-associated proteins such as catenins, cadherins, nectin-3 and afadin. These findings highlight the important role of MAPK signaling in sustaining both apical ES and the TJ dynamics (Figure 10.2).
Addition of anti-TIM3 or anti-TIGIT Antibodies to anti-PD1 Blockade Augments Human T cell Adoptive Cell Transfer
Published in OncoImmunology, 2021
Marina Martinez, Soyeon Kim, Naomi St. Jean, Shaun O’Brien, Lurong Lian, Jing Sun, Raluca I. Verona, Edmund Moon
We measured the expression of PD-L1 and the three reported ligands of TIGIT (CD155 (PVR), CD112 (PVRL2, Nectin-2), and CD113 (PVRL3, Nectin-3)) on the CD45 negative tumor cells (CBG positive) from the flank tumor digests and observed upregulation of all four of these ligands in the tumors that were treated with Ly95 T cells and PD1 blockade (Figure 7d). We also measured the expression of the receptors CD226 and CD96 which have been reported to co-express and interact with TIGIT. CD226 counterbalances TIGIT suppression and CD96 competes with CD226 for ligand binding36 Cryopreserved Ly95 T cells had dual expression of both CD226 and CD96 (47.7%) (Figure 8a first dotplot) with PD1+ Ly95 T cells (Figure 8a second dotplot) having greater dual expression than PD1- counterparts (Figure 8a third dotplot). (80.3% vs. 46.2%). Ly95 TILs had much lower expression of both receptors (5.2%). (Figure 8a, dot plots in blue square; Figure 8b left group of bars), PD1 blockade led to significant upregulation of both CD226 and CD96 (Figure 8a, dot plots in purple square; Figure 8b, red bars).
Deficiency of host CD96 and PD-1 or TIGIT enhances tumor immunity without significantly compromising immune homeostasis
Published in OncoImmunology, 2018
Heidi Harjunpää, Stephen J. Blake, Elizabeth Ahern, Stacey Allen, Jing Liu, Juming Yan, Viviana Lutzky, Kazuyoshi Takeda, Amy Roman Aguilera, Camille Guillerey, Deepak Mittal, Xian Yang Li, William C. Dougall, Mark J. Smyth, Michele W. L. Teng
CD96 (TACTILE) and TIGIT (T-cell immunoglobulin and ITIM domain) belong to an emerging family of cell surface receptors that bind to ligands of the nectin and nectin-like family.14 The expression patterns of CD96 and TIGIT are broadly similar between mouse and humans, where they are mainly found on peripheral T cells including regulatory T cells (Tregs) and NK cells, particularly following activation.15-19 CD155 (necl-5; PVR) is the main ligand that binds CD96 and TIGIT in both humans and mice.17,18,20 CD155 also binds the activating receptor DNAM-1 (CD226), which like CD96 and TIGIT, is expressed on T and NK cells.15,21,22 In mice, CD96 also binds CD111 (nectin-1), which has been demonstrated to enhance T cell and NK cell adhesion17,20 while TIGIT binds CD112 (PVRL2, nectin-2) and CD113 (PVRL3, nectin-3).18,19 Recently it was reported that CD112R, a novel co-inhibitory receptor which is preferentially expressed on human T cells binds CD112 with high affinity and competes with CD226 to bind CD112.23
Detection of Proteins Associated with Extracellular Matrix Regulation in the Aqueous Humour of Patients with Primary Glaucoma
Published in Current Eye Research, 2019
Sampath Nikhalashree, Ronnie George, Balekudaru Shantha, Vijaya Lingam, Wadke Vidya, Manish Panday, Konerirajapuram Natarajan Sulochana, Karunakaran Coral
There were few unique sets of proteins identified in our study that were not reported earlier in AH studies and they include, afadin, an actin filament-binding and a neuronal intercellular adhesion protein, known to interact with Nectin 3. They also interact with JAG1 involved in the differentiation of rat lens development.37 Syntabulin, also known as golsyn (human Golgi-localized syntaphilin-related protein) functions as a vesicular transporter in mice brain, and this gene is mapped to human chromosome 8q23, the loci responsible for primary open-angle glaucoma.38 Calsequestrin and sarcalumenin are calcium-binding proteins, and they might play a role in neurodegeneration based on calcium-dependent mechanism.39