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Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis
Endometriosis is a hormonal disease, as well as a chronic inflammatory disease. While various immune cells are documented to be involved in endometriosis, there is a wanton lack of a bigger picture on how these cells are coordinated to work concertedly. Since endometriotic lesions experience cyclica...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767909/ https://www.ncbi.nlm.nih.gov/pubmed/33381124 http://dx.doi.org/10.3389/fimmu.2020.610963 |
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author | Xiao, Fengyi Liu, Xishi Guo, Sun-Wei |
author_facet | Xiao, Fengyi Liu, Xishi Guo, Sun-Wei |
author_sort | Xiao, Fengyi |
collection | PubMed |
description | Endometriosis is a hormonal disease, as well as a chronic inflammatory disease. While various immune cells are documented to be involved in endometriosis, there is a wanton lack of a bigger picture on how these cells are coordinated to work concertedly. Since endometriotic lesions experience cyclical bleeding, they are fundamentally wounds that undergo repeated tissue injury and repair (ReTIAR). In this study, we attempted to characterize the role of platelets and regulatory T cells (Tregs) in modulating the lesional immune microenvironment and its subsequent effects on lesional progression and fibrogenesis. Through two mouse experiments, we show that, by disrupting predominantly a type 2 immune response in lesional microenvironment, both platelets and Tregs depletion decelerated lesional progression and fibrogenesis, likely through the suppression of the TGF-β1/Smad3 and PDGFR-β/PI3K/Akt signaling pathways. In particular, platelet depletion resulted in significantly reduced lesional expression of thymic stromal lymphopoietin (TSLP), leading to reduced aggregation of macrophages and alternatively activated (M2) macrophages, and of Tregs, T helper 2 (Th2) and Th17 cells but increased aggregation of Th1 cells, in lesions, which, in turn, yields retarded fibrogenesis. Similarly, Tregs depletion resulted in suppression of platelet aggregation, and reduced aggregation of M2 macrophages, Th2 and Th17 cells but increased aggregation of Th1 cells, in lesions. Thus, both platelet and Tregs depletion decelerated lesional progression and fibrogenesis by disrupting predominantly a type 2 immunity in lesional microenvironment. Taken together, this suggests that both platelets and Tregs may induce a type 2 immunity in lesional microenvironment that is conducive to lesional progression and fibrogenesis. |
format | Online Article Text |
id | pubmed-7767909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77679092020-12-29 Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis Xiao, Fengyi Liu, Xishi Guo, Sun-Wei Front Immunol Immunology Endometriosis is a hormonal disease, as well as a chronic inflammatory disease. While various immune cells are documented to be involved in endometriosis, there is a wanton lack of a bigger picture on how these cells are coordinated to work concertedly. Since endometriotic lesions experience cyclical bleeding, they are fundamentally wounds that undergo repeated tissue injury and repair (ReTIAR). In this study, we attempted to characterize the role of platelets and regulatory T cells (Tregs) in modulating the lesional immune microenvironment and its subsequent effects on lesional progression and fibrogenesis. Through two mouse experiments, we show that, by disrupting predominantly a type 2 immune response in lesional microenvironment, both platelets and Tregs depletion decelerated lesional progression and fibrogenesis, likely through the suppression of the TGF-β1/Smad3 and PDGFR-β/PI3K/Akt signaling pathways. In particular, platelet depletion resulted in significantly reduced lesional expression of thymic stromal lymphopoietin (TSLP), leading to reduced aggregation of macrophages and alternatively activated (M2) macrophages, and of Tregs, T helper 2 (Th2) and Th17 cells but increased aggregation of Th1 cells, in lesions, which, in turn, yields retarded fibrogenesis. Similarly, Tregs depletion resulted in suppression of platelet aggregation, and reduced aggregation of M2 macrophages, Th2 and Th17 cells but increased aggregation of Th1 cells, in lesions. Thus, both platelet and Tregs depletion decelerated lesional progression and fibrogenesis by disrupting predominantly a type 2 immunity in lesional microenvironment. Taken together, this suggests that both platelets and Tregs may induce a type 2 immunity in lesional microenvironment that is conducive to lesional progression and fibrogenesis. Frontiers Media S.A. 2020-12-14 /pmc/articles/PMC7767909/ /pubmed/33381124 http://dx.doi.org/10.3389/fimmu.2020.610963 Text en Copyright © 2020 Xiao, Liu and Guo http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Xiao, Fengyi Liu, Xishi Guo, Sun-Wei Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis |
title | Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis |
title_full | Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis |
title_fullStr | Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis |
title_full_unstemmed | Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis |
title_short | Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis |
title_sort | platelets and regulatory t cells may induce a type 2 immunity that is conducive to the progression and fibrogenesis of endometriosis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767909/ https://www.ncbi.nlm.nih.gov/pubmed/33381124 http://dx.doi.org/10.3389/fimmu.2020.610963 |
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