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Regulatory T cells regulate blastemal proliferation during zebrafish caudal fin regeneration.

ABSTRACT: The role of T cells in appendage regeneration remains unclear. In this study, we revealed an important role for regulatory T cells (Tregs), a subset of T cells that regulate tolerance and tissue repair, in the epimorphic regeneration of zebrafish caudal fin tissue. Upon amputation, fin tissue-resident Tregs infiltrate into the blastema, a population of progenitor cells that produce new fin tissues. Conditional genetic ablation of Tregs attenuates blastemal cell proliferation during fin regeneration. Blastema-infiltrating Tregs upregulate the expression of igf2a and igf2b, and pharmacological activation of IGF signaling restores blastemal proliferation in Treg-ablated zebrafish. These findings further extend our understandings of Treg function in tissue regeneration and repair.

SUBMITTER: Hui SP

PROVIDER: S-EPMC9429828 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Regulatory T cells regulate blastemal proliferation during zebrafish caudal fin regeneration.

Hui Subhra P SP Sugimoto Kotaro K Sheng Delicia Z DZ Kikuchi Kazu K

Frontiers in immunology 20220817

The role of T cells in appendage regeneration remains unclear. In this study, we revealed an important role for regulatory T cells (Tregs), a subset of T cells that regulate tolerance and tissue repair, in the epimorphic regeneration of zebrafish caudal fin tissue. Upon amputation, fin tissue-resident Tregs infiltrate into the blastema, a population of progenitor cells that produce new fin tissues. Conditional genetic ablation of Tregs attenuates blastemal cell proliferation during fin regenerat ...[more]

PMID: 36059461

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Project description:Aquatic vertebrates possess diverse types of sensory cells in their skin to detect stimuli in the water. In the adult zebrafish, a common model organism, the presence of such cells in fins has only rarely been studied. Here, we identified scattered serotonin (5-HT)-positive cells in the epidermis of the caudal fin. These cells were distinct from keratinocytes as revealed by their low immunoreactivity for cytokeratin and desmosome markers. Instead, they were detected by Calretinin (Calbindin-2) and Synaptic vesicle glycoprotein 2 (SV2) antibodies, indicating a calcium-regulated neurosecretory activity. Consistently, electron microscopy revealed abundant secretory organelles in desmosome-negative cells in the fin epidermis. Based on the markers, 5-HT, Calretinin and SV2, we referred to these cells as HCS-cells. We found that HCS-cells were spread throughout the entire caudal fin at an average density of 140 cells per mm2 on each fin surface. These cells were strongly enriched at ray bifurcations in wild type fins, as well as in elongated fins of another longfin mutant fish. To determine whether hydrodynamics play a role in the distribution of HCS-cells, we used an interdisciplinary approach and performed kinematic analysis. Measurements of particle velocity with a fin model revealed differences in fluid velocities between bifurcated rods and adjacent non-bifurcated regions. Therefore the accumulation of HCS-cells near bone bifurcations may be a biological adaptation for sensing of water parameters. The significance of this HCS-cell pattern is reinforced by the fact, that it is reestablished in the regenerated fin after amputation. Regeneration of HCS-cells was not impaired by the chemical inhibition of serotonin synthesis, suggesting that this neurotransmitter is not essential for the restorative process. In conclusion, our study identified a specific population of solitary paraneurons in the zebrafish fin, whose distribution correlates with fluid dynamics.

Dataset Information

Regulatory T cells regulate blastemal proliferation during zebrafish caudal fin regeneration.

Publications

Regulatory T cells regulate blastemal proliferation during zebrafish caudal fin regeneration.

Similar Datasets

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