Similar Datasets
Project description:In contrast to adult mammals, adult zebrafish are able to fully regenerate injured cardiac tissue, and this regeneration process requires an adequate and tightly controlled immune response. However, which immune aspects drive particular aspects of the regenerative response are unclear. Here, we report the participation and requirement of the antigen presentation-adaptive immunity axis during zebrafish cardiac regeneration. We found that, in addition to immune cells, endocardial cells start expressing antigen presentation genes following the initial innate immune response. Consistent with this finding, we observed that helper T cells, a.k.a. Cd4+ T cells, are closely associated with phosphoERK+ (pERK+) (i.e., activated) endocardial cells at these stages. We inactivated major histocompatibility complex (MHC) class II antigen presentation by generating cd74a; cd74b double mutants, which display a defective immune response. In these mutants, both Cd4+ T cells and pERK+ endocardial cells fail to efficiently infiltrate the injured tissue. Notably, this model of compromised antigen presentation exhibits additional defects in cardiac regeneration including reduced cardiomyocyte dedifferentiation and proliferation. Altogether, these findings reveal a necessary role for antigen presentation during zebrafish cardiac regeneration and point to an immune crosstalk between T cells and endocardial cells, thereby further establishing a link between the adaptive immune response and tissue regeneration.
2024-03-06 | GSE230669 | GEO
Project description:In contrast to adult mammals, adult zebrafish are able to fully regenerate injured cardiac tissue, and this regeneration process requires an adequate and tightly controlled immune response. However, which immune aspects drive particular aspects of the regenerative response are unclear. Here, we report the participation and requirement of the antigen presentation-adaptive immunity axis during zebrafish cardiac regeneration. We found that, in addition to immune cells, endocardial cells start expressing antigen presentation genes following the initial innate immune response. Consistent with this finding, we observed that helper T cells, a.k.a. Cd4+ T cells, are closely associated with phosphoERK+ (pERK+) (i.e., activated) endocardial cells at these stages. We inactivated major histocompatibility complex (MHC) class II antigen presentation by generating cd74a; cd74b double mutants, which display a defective immune response. In these mutants, both Cd4+ T cells and pERK+ endocardial cells fail to efficiently infiltrate the injured tissue. Notably, this model of compromised antigen presentation exhibits additional defects in cardiac regeneration including reduced cardiomyocyte dedifferentiation and proliferation. Altogether, these findings reveal a necessary role for antigen presentation during zebrafish cardiac regeneration and point to an immune crosstalk between T cells and endocardial cells, thereby further establishing a link between the adaptive immune response and tissue regeneration.
2024-03-06 | GSE232060 | GEO
Project description:In contrast to adult mammals, adult zebrafish are able to fully regenerate injured cardiac tissue, and this regeneration process requires an adequate and tightly controlled immune response. However, which immune aspects drive particular aspects of the regenerative response are unclear. Here, we report the participation and requirement of the antigen presentation-adaptive immunity axis during zebrafish cardiac regeneration. We found that, in addition to immune cells, endocardial cells start expressing antigen presentation genes following the initial innate immune response. Consistent with this finding, we observed that helper T cells, a.k.a. Cd4+ T cells, are closely associated with phosphoERK+ (pERK+) (i.e., activated) endocardial cells at these stages. We inactivated major histocompatibility complex (MHC) class II antigen presentation by generating cd74a; cd74b double mutants, which display a defective immune response. In these mutants, both Cd4+ T cells and pERK+ endocardial cells fail to efficiently infiltrate the injured tissue. Notably, this model of compromised antigen presentation exhibits additional defects in cardiac regeneration including reduced cardiomyocyte dedifferentiation and proliferation. Altogether, these findings reveal a necessary role for antigen presentation during zebrafish cardiac regeneration and point to an immune crosstalk between T cells and endocardial cells, thereby further establishing a link between the adaptive immune response and tissue regeneration.
2024-03-06 | GSE232059 | GEO
Project description:Endocardial cells function as antigen-presenting cells to promote zebrafish heart regeneration
| PRJNA962109 | ENA
Project description:Endocardial cells function as antigen-presenting cells to promote zebrafish heart regeneration
| PRJNA970722 | ENA
Project description:Endocardial cells function as antigen-presenting cells to promote zebrafish heart regeneration [dst173_scrnaseq]
| PRJNA970720 | ENA
Project description:Endocardial cells function as antigen-presenting cells to promote zebrafish heart regeneration [dst93_scrnaseq]
| PRJNA970725 | ENA
Project description:Heart regeneration requires replenishment of lost cardiomyocytes (CMs) and cells of the endocardial lining. However, the signaling regulation and transcriptional control of myocardial dedifferentiation and endocardial activation are incompletely understood during cardiac regeneration. Here, we report that T-Box Transcription Factor 20 (Tbx20) is induced rapidly in the myocardial wound edge in response to various sources of cardiac damages in zebrafish. Inducing Tbx20 specifically in the adult myocardium promotes injury-induced CM proliferation through CM dedifferentiation, leading to loss of CM cellular contacts and re-expression of cardiac embryonic or fetal gene programs. Unexpectedly, we identify that myocardial Tbx20 induction activates the endocardium at the injury site with enhanced endocardial cell extension and proliferation, where it induces the endocardial Bone morphogenetic protein 6 (Bmp6) signaling. Pharmacologically inactivating endocardial Bmp6 signaling reduces expression of its targets, Id1 and Id2b, attenuating the increased endocardial regeneration in tbx20-overexpressing hearts. Altogether, our study demonstrates that Tbx20 induction promotes adult heart regeneration by inducing cardiomyocyte dedifferentiation as well as non-cell-autonomously enhancing endocardial cell regeneration.
| S-EPMC7417483 | biostudies-literature
Project description:In mammals, dendritic cells (DCs) form the key link between the innate and adaptive immune systems. DCs act as immune sentries in various tissues and, upon encountering pathogen, engulf and traffic foreign antigen to secondary lymphoid tissues, stimulating antigen-specific T lymphocytes. Although DCs are of fundamental importance in orchestrating the mammalian immune response, their presence and function in nonmammalian vertebrates is largely unknown. Because teleosts possess one of the earliest recognizable adaptive immune systems, we sought to identify antigen-presenting cells (APCs) in the zebrafish to better understand the potential origins of DCs and their evolutionary relationship to lymphocytes. Here we present the identification and characterization of a zebrafish APC subset strongly resembling mammalian DCs. Rare DCs are present in various adult tissues, and can be enriched by their affinity for the lectin peanut agglutinin (PNA). We show that PNA(hi) myeloid cells possess the classical morphological features of mammalian DCs as revealed by histochemical and ultrastructural analyses, phagocytose-labeled bacterial preparations in vivo, and exhibit expression of genes associated with DC function and antigen presentation, including il12, MHC class II invariant chain iclp1, and csf1r. Importantly, we show that PNA(hi) cells can activate T lymphocytes in an antigen-dependent manner. Together, these studies suggest that the cellular constituents responsible for antigen presentation are remarkably conserved from teleosts to mammals, and indicate that the zebrafish may serve as a unique model to study the origin of APC subsets and their evolutionary role as the link between the innate and adaptive immune systems.
| S-EPMC2936643 | biostudies-other
Project description:NKT cells have been shown to promote peripheral tolerance in a number of model systems, yet the processes by which they exert their regulatory effects remain poorly understood. Here, we show that soluble factors secreted by human NKT cells instruct human peripheral blood monocytes to differentiate into myeloid APCs that have suppressive properties. NKT instructed monocytes acquired a cell surface phenotype resembling myeloid DCs. However, whereas control DCs that were generated by culturing monocytes with recombinant GM-CSF and IL-4 had a proinflammatory phenotype characterized by the production of IL-12 with little IL-10, NKT-instructed APCs showed the opposite cytokine production profile of high IL-10 with little or no IL-12. The control DCs efficiently stimulated peripheral blood T cell IFN-gamma secretion and proliferation, whereas NKT-instructed APCs silenced these T cell responses. Exposure to NKT cell factors had a dominant effect on the functional properties of the DCs, since DCs differentiated by recombinant GM-CSF and IL-4 in the presence of NKT cell factors inhibited T cell responses. To confirm their noninflammatory effects, NKT-instructed APCs were tested in an in vivo assay that depends on the activation of antigen-specific human T cells. Control DCs promoted substantial tissue inflammation; however, despite a marked neutrophilic infiltrate, there was little edema in the presence of NKT-instructed APCs, suggesting the inflammatory cascade was held in check. These results point to a novel pathway initiated by NKT cells that can contribute to the regulation of human antigen-specific Th1 responses.
| S-EPMC2752012 | biostudies-literature