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 [dst93_scrnaseq]
| PRJNA970725 | ENA
Project description:Endocardial cells function as antigen-presenting cells to promote zebrafish heart regeneration [dst173_scrnaseq]
| PRJNA970720 | 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:During cardiac development, endocardial cells (EdCs) produce growth factors to promote myocardial morphogenesis and growth. In particular, EdCs produce neuregulin which is required for ventricular cardiomyocytes (CMs) to seed the multicellular ridges known as trabeculae. Defects in neuregulin signaling, or in endocardial sprouting toward CMs, cause hypotrabeculation. However, the mechanisms underlying endocardial sprouting remain largely unknown. Here, we first show by live imaging in zebrafish embryos that EdCs interact with CMs via dynamic membrane protrusions. After touching CMs, these protrusions remain in close contact with their target despite the vigorous cardiac contractions. Loss of the CM-derived peptide Apelin, or of the Apelin receptor, which is expressed in EdCs, leads to reduced endocardial sprouting and hypotrabeculation. Mechanistically, neuregulin signaling requires endocardial protrusions to induce extracellular signal-regulated kinase (Erk) activity in CMs and trigger their delamination. Altogether, these data show that Apelin signaling-dependent endocardial protrusions modulate CM behavior during trabeculation.
| S-EPMC8916774 | biostudies-literature