Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue
γδ T cells, a small subset of T cells in blood, play a substantial role in influencing immunoregulatory and inflammatory processes. The functional impact of γδ T cells on angiogenesis in ischemic muscle tissue has never been reported and is the topic of the present work. Femoral artery ligation (FAL...
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2022-04-01
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author | Christoph Arnholdt Konda Kumaraswami Philipp Götz Matthias Kübler Manuel Lasch Elisabeth Deindl |
author_facet | Christoph Arnholdt Konda Kumaraswami Philipp Götz Matthias Kübler Manuel Lasch Elisabeth Deindl |
author_sort | Christoph Arnholdt |
collection | DOAJ |
description | γδ T cells, a small subset of T cells in blood, play a substantial role in influencing immunoregulatory and inflammatory processes. The functional impact of γδ T cells on angiogenesis in ischemic muscle tissue has never been reported and is the topic of the present work. Femoral artery ligation (FAL) was used to induce angiogenesis in the lower leg of γδ T cell depleted mice and wildtype and isotype antibody-treated control groups. Gastrocnemius muscle tissue was harvested 3 and 7 days after FAL and assessed using (immuno-)histological analyses. Hematoxylin and Eosin staining showed an increased area of tissue damage in γδ T cell depleted mice 7 days after FAL. Impaired angiogenesis was demonstrated by lower capillary to muscle fiber ratio and decreased number of proliferating endothelial cells (CD31<sup>+</sup>/BrdU<sup>+</sup>). γδ T cell depleted mice showed an increased number of total leukocytes (CD45<sup>+</sup>), neutrophils (MPO<sup>+</sup>) and neutrophil extracellular traps (NETs) (MPO<sup>+</sup>/CitH3<sup>+</sup>), without changes in the neutrophils to NETs ratio. Moreover, the depletion resulted in a higher macrophage count (DAPI/CD68<sup>+</sup>) caused by an increase in inflammatory M1-like macrophages (CD68<sup>+</sup>/MRC1<sup>−</sup>). Altogether, we show that depletion of γδ T cells leads to increased accumulation of leukocytes and M1-like macrophages, along with impaired angiogenesis. |
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spelling | doaj.art-5c9e799de3004ba7a15314039d15d73b2023-11-23T07:59:56ZengMDPI AGCells2073-44092022-04-01119149010.3390/cells11091490Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle TissueChristoph Arnholdt0Konda Kumaraswami1Philipp Götz2Matthias Kübler3Manuel Lasch4Elisabeth Deindl5Walter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, Germanyγδ T cells, a small subset of T cells in blood, play a substantial role in influencing immunoregulatory and inflammatory processes. The functional impact of γδ T cells on angiogenesis in ischemic muscle tissue has never been reported and is the topic of the present work. Femoral artery ligation (FAL) was used to induce angiogenesis in the lower leg of γδ T cell depleted mice and wildtype and isotype antibody-treated control groups. Gastrocnemius muscle tissue was harvested 3 and 7 days after FAL and assessed using (immuno-)histological analyses. Hematoxylin and Eosin staining showed an increased area of tissue damage in γδ T cell depleted mice 7 days after FAL. Impaired angiogenesis was demonstrated by lower capillary to muscle fiber ratio and decreased number of proliferating endothelial cells (CD31<sup>+</sup>/BrdU<sup>+</sup>). γδ T cell depleted mice showed an increased number of total leukocytes (CD45<sup>+</sup>), neutrophils (MPO<sup>+</sup>) and neutrophil extracellular traps (NETs) (MPO<sup>+</sup>/CitH3<sup>+</sup>), without changes in the neutrophils to NETs ratio. Moreover, the depletion resulted in a higher macrophage count (DAPI/CD68<sup>+</sup>) caused by an increase in inflammatory M1-like macrophages (CD68<sup>+</sup>/MRC1<sup>−</sup>). Altogether, we show that depletion of γδ T cells leads to increased accumulation of leukocytes and M1-like macrophages, along with impaired angiogenesis.https://www.mdpi.com/2073-4409/11/9/1490angiogenesisγδ T cellsgamma delta T cellsproliferationmacrophagesmacrophage polarization |
spellingShingle | Christoph Arnholdt Konda Kumaraswami Philipp Götz Matthias Kübler Manuel Lasch Elisabeth Deindl Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue Cells angiogenesis γδ T cells gamma delta T cells proliferation macrophages macrophage polarization |
title | Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue |
title_full | Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue |
title_fullStr | Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue |
title_full_unstemmed | Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue |
title_short | Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue |
title_sort | depletion of γδ t cells leads to reduced angiogenesis and increased infiltration of inflammatory m1 like macrophages in ischemic muscle tissue |
topic | angiogenesis γδ T cells gamma delta T cells proliferation macrophages macrophage polarization |
url | https://www.mdpi.com/2073-4409/11/9/1490 |
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