Chronic wounds suffer from impaired healing due to microbial attack and poor vascular growth. Thermoresponsive hydrogels gained attention in wound dressing owing to their gelation at physiological temperature enabling them to take the shape of asymmetric wounds. The present study delineates the development of thermoresponsive hydrogel (MCK), from hair-derived keratin (K) and methylcellulose (MC) in the presence of sodium sulfate.
View Article and Find Full Text PDFMol Immunol
February 2024
Butyrophilin-like 2 (BTNL2) is a T cell inhibitory molecule that interacts with unknown binding partners to modulate the immune response in a number of inflammatory and autoimmune diseases. In this study, we found that the inhibitory effects of BTNL2 on T cell activation and effector functions can be executed by its N-terminal IgV domain (BTNL2 IgV1) alone. Structure-guided mutation of key residues on BTNL2 IgV1 based on known receptor-ligand interfaces involving immunoglobulin superfamily members revealed that BTNL2 uses a non-canonical binding interface with its putative receptor.
View Article and Find Full Text PDFA soluble isoform of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has been found in the serum of healthy individuals and alterations in its expression level have been linked with the development and progression of various cancers. Conventionally, soluble CTLA-4 (sCTLA-4) has been quantified by techniques such as ELISA, western blot, and flow cytometry, which however are time-consuming, highly expensive and require large sample volumes. Therefore, rapid, cost-effective and real-time monitoring of soluble CTLA-4 levels is much needed to facilitate timely diagnosis of a worsening disease and help patient selection for immunotherapeutic interventions in cancer.
View Article and Find Full Text PDFImmunotherapeutic modulation of antigen-specific T-cell responses instead of the whole repertoire helps avoid immune-related adverse events. We have developed an artificial antigen-presenting system (aAPS) where multiple copies of a multimeric peptide-MHC class I complex presenting a murine class I MHC restricted ovalbumin-derived peptide (signal 1), along with a costimulatory ligand (signal 2) are chemically conjugated to a dextran backbone. Cognate naive CD8 T cells, when treated with this aAPS underwent significant expansion and showed an activated phenotype.
View Article and Find Full Text PDFAppl Microbiol Biotechnol
November 2023
The Big Grain1 (BG1) gene of rice (Oryza sativa L.) is reported to increase the yield of rice crops; however, its molecular mechanism is largely concealed. To explore its functional prospects, we have taken a structure-function-based approach.
View Article and Find Full Text PDFChronic wounds are the outcome of an imbalanced inflammatory response caused by sustenance of immune microenvironment. In this context, tissue engineered graft played great role in healing wounds but faced difficulty in scar remodelling, immune rejection and poor vascularization. All the limitations faced are somewhere linked with the immune cells involved in healing.
View Article and Find Full Text PDFHLA-A*02:01:01:241 differs from HLA-A*02:01:01:01 by a single nucleotide substitution at position 178 in intron 1.
View Article and Find Full Text PDFEndometriosis is a debilitating gynecological disorder in women of reproductive age. Laparoscopy, a minimally invasive surgical procedure, provides a definitive diagnosis of the disease. Current treatments, including hormonal therapy and pain medication, are often associated with undesirable side effects limiting their long-term usage.
View Article and Find Full Text PDFCadherins are a family of cell surface glycoproteins that mediate Ca-dependent cell to cell adhesion. They organize to form large macromolecular assemblies at the junctions of cells in order to form and maintain the integrity of tissue structures, thereby playing an indispensable role in the multicellular organization. Notably, a large body of research on E- and N-cadherin, the two most widely studied members of the cadherin superfamily, suggest for homophilic associations among them to drive cell adhesion.
View Article and Find Full Text PDFInt J Biol Macromol
June 2022
Tuberculosis, caused by Mycobacterium tuberculosis, is predominantly a disease of the lungs acquired by inhaling mycobacteria from infected individuals via airborne droplets. In order to facilitate their entry into the alveolar macrophages, mycobacteria have a collection of pathogen-associated molecular patterns (PAMPs) on their surface that are known to detect certain pattern recognition receptors present on the surface of host cells. A major group of these PAMPs includes mycobacterial lipoproteins, of which, the 19 kDa surface antigen LpqH, has been reported to play a critical role in both host-pathogen interactions as well as pleiotropic immune regulation.
View Article and Find Full Text PDFAntigen-specificity of T cells provides important clues to the pathogenesis of T cell-mediated autoimmune diseases and immune-evasion strategies of tumors. Identification of T cell clones involved in autoimmunity or cancer is achieved with soluble peptide-MHC (pMHC) complex multimers. Importantly, these complexes can also be used to manipulate disease-relevant T cells to restore homeostasis of T cell-mediated immune response.
View Article and Find Full Text PDFConvalescent plasma therapy provides a useful therapeutic tool to treat infectious diseases, especially where no specific therapeutic strategies have been identified. The ongoing pandemic puts back the spotlight on this age-old method as a viable treatment option. In this review, we discuss the usage of this therapy in different diseases including COVID-19, and the possible mechanisms of action.
View Article and Find Full Text PDFEndometrial disorders collectively encompass a broad spectrum of pathologies, including but not limited to endometriosis, endometrial cancer and endometritis. The current therapeutic management of these diseases is associated with several limitations. This has prompted interest in the use of plant-based bioactive compounds as alternative strategies to achieve high therapeutic efficacy and avoid adverse effects.
View Article and Find Full Text PDFT cell costimulation is mediated by the interaction of a number of receptors and ligands present on the surface of the T cell and antigen-presenting cell, respectively. Stimulatory or inhibitory signals from these receptor-ligand interactions work in tandem to preserve immune homeostasis. BTNL2 is a type-1 membrane protein that provides inhibitory signal to T cells and plays an important role in several inflammatory and autoimmune diseases.
View Article and Find Full Text PDFCancer Rep (Hoboken)
August 2019
Background: With the recent advances in the understanding of the interaction of the immune system with developing tumor, it has become imperative to consider the immunological parameters for both cancer diagnosis and disease prognosis. Additionally, in the era of emerging immunotherapeutic strategies in cancer, it is very important to follow the treatment outcome and also to predict the correct immunotherapeutic strategy in individual patients. There being enormous heterogeneity among tumors at different sites or between primary and metastatic tumors in the same individual, or interpatient heterogeneity, it is very important to study the tumor-immune interaction in the tumor microenvironment and beyond.
View Article and Find Full Text PDFDue to their ability to knock down the expression of any gene, siRNAs have been heralded as ideal candidates for treating a wide variety of diseases, including those involving "undruggable" targets. However, the therapeutic potential of siRNAs remains severely limited by a lack of effective delivery vehicles. Recently, lipid nanoparticles (LNPs) containing ionizable cationic lipids have been developed for hepatic siRNA delivery.
View Article and Find Full Text PDFType 1 diabetes is characterized by T-cell-mediated destruction of the insulin-producing β cells in pancreatic islets. A number of islet antigens recognized by CD8 T cells that contribute to disease pathogenesis in non-obese diabetic (NOD) mice have been identified; however, the antigenic specificities of the majority of the islet-infiltrating cells have yet to be determined. The primary goal of the current study was to identify candidate antigens based on the level and specificity of expression of their genes in mouse islets and in the mouse β cell line MIN6.
View Article and Find Full Text PDFSelf-reactive T cells must escape thymic negative selection to mediate pathogenic autoimmunity. In the NOD mouse model of autoimmune diabetes, several β cell-cytotoxic CD8 T cell populations are known, with the most aggressive of these represented by AI4, a T cell clone with promiscuous Ag-recognition characteristics. We identified a long-elusive β cell-specific ligand for AI4 as an unusually short H-2D(b)-binding 7-mer peptide lacking a C-terminal anchor residue and derived from the insulin A chain (InsA14-20).
View Article and Find Full Text PDFCD8⁺ T cells specific for islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) have been implicated in type 1 diabetes in both humans and non-obese diabetic (NOD) mice, in which T cells specific for IGRP₂₀₆₋₂₁₄ are highly prevalent. We sought to manipulate these pathogenic T cells by exploiting the ability of steady-state dendritic cells (DCs) to present antigens in a tolerogenic manner. The endocytic receptor DEC-205 was utilized to deliver an IGRP₂₀₆₋₂₁₄ mimotope to DCs in NOD mice, and the impact of this delivery on a polyclonal population of endogenous islet-reactive cognate T cells was determined.
View Article and Find Full Text PDFType 1 diabetes is an autoimmune disease characterized by T cell responses to β cell Ags, including insulin. Investigations employing the NOD mouse model of the disease have revealed an essential role for β cell-specific CD8(+) T cells in the pathogenic process. As CD8(+) T cells specific for β cell Ags are also present in patients, these reactivities have the potential to serve as therapeutic targets or markers for autoimmune activity.
View Article and Find Full Text PDFVibrio cholerae hemolysin (HlyA) displays bipartite property while supervising macrophages (MΦ). The pore-forming toxin causes profound apoptosis within 3 h of exposure and in parallel supports activation of the defying MΦ. HlyA-induced apoptosis of MΦ remains steady for 24 h, is Toll-like receptor (TLR)-independent, and is driven by caspase-9 and caspase-7, thus involving the mitochondrial or intrinsic pathway.
View Article and Find Full Text PDFPeptide-MHC (pMHC) multimers, in addition to being tools for tracking and quantifying antigen-specific T cells, can mediate downstream signaling after T-cell receptor engagement. In the absence of costimulation, this can lead to anergy or apoptosis of cognate T cells, a property that could be exploited in the setting of autoimmune disease. Most studies with class I pMHC multimers used noncovalently linked peptides, which can allow unwanted CD8(+) T-cell activation as a result of peptide transfer to cellular MHC molecules.
View Article and Find Full Text PDFThe hemolysin oligomer promotes the proliferation of B-1a cells and the expression of CD25, which is indicative of cell activation, on B-1a cells. The upregulation of CD86 induced by the oligomer showed its selective bias for the B7-2 member of B7 family while the monomer failed to induce these effects. The oligomer induced the expression of CXCR3, associated with B cell activation, while the monomer induced the expression of CXCL4, a powerful angiostatic chemokine.
View Article and Find Full Text PDFVibrio cholerae hemolysin (HlyA) can exist as a monomer with hemolytic activity and an oligomer that agglutinates erythrocytes. Biochemical differences accompanying the change in state of aggregation led us to weigh possible differences between the two forms from mucosal immunoregulation perspective. HlyA oligomer-treated murine B-1a cells up-regulated TLR2 and involved the signaling molecules MyD88, TRAF6 and NF-kappaB.
View Article and Find Full Text PDFPorin of Shigella dysenteriae type 1 coexpressed Toll-like receptor (TLR) 2 and TLR6 on peritoneal cavity (PerC) macrophages (MPhi) of C57BL/6 mice implicating that both the TLRs are essential as a combinatorial repertoire to recognize the protein. Besides TLRs, mRNA for MyD88 and TRAF6, and nuclear translocation of NF-kappaB were enhanced that indicate their involvement in tandem in the activity of porin. The protein selectively up-regulated CD80 on the activated MPhi together with MHC class II molecule and CD40, and had no effect on CD86 expression.
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