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...

Full description

Bibliographic Details
Main Authors: Christoph Arnholdt, Konda Kumaraswami, Philipp Götz, Matthias Kübler, Manuel Lasch, Elisabeth Deindl
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/9/1490
_version_ 1797505250366586880
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.
first_indexed 2024-03-10T04:15:56Z
format Article
id doaj.art-5c9e799de3004ba7a15314039d15d73b
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-10T04:15:56Z
publishDate 2022-04-01
publisher MDPI AG
record_format Article
series Cells
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
work_keys_str_mv AT christopharnholdt depletionofgdtcellsleadstoreducedangiogenesisandincreasedinfiltrationofinflammatorym1likemacrophagesinischemicmuscletissue
AT kondakumaraswami depletionofgdtcellsleadstoreducedangiogenesisandincreasedinfiltrationofinflammatorym1likemacrophagesinischemicmuscletissue
AT philippgotz depletionofgdtcellsleadstoreducedangiogenesisandincreasedinfiltrationofinflammatorym1likemacrophagesinischemicmuscletissue
AT matthiaskubler depletionofgdtcellsleadstoreducedangiogenesisandincreasedinfiltrationofinflammatorym1likemacrophagesinischemicmuscletissue
AT manuellasch depletionofgdtcellsleadstoreducedangiogenesisandincreasedinfiltrationofinflammatorym1likemacrophagesinischemicmuscletissue
AT elisabethdeindl depletionofgdtcellsleadstoreducedangiogenesisandincreasedinfiltrationofinflammatorym1likemacrophagesinischemicmuscletissue