Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls
Summary: Amyotrophic lateral sclerosis (ALS) is a disorder with immune alterations that augment disease severity. M2 macrophages benefit diabetic and nephrotic mice by suppressing the pro-inflammatory state. However, neither have M2 cells been investigated in ALS nor have human induced pluripotent s...
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doaj-67b09fdc1b1d4b14a65212fba39aef582020-11-25T03:12:43ZengElsevieriScience2589-00422020-06-01236101192Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy ControlsWeihua Zhao0David R. Beers1Jason R. Thonhoff2Aaron D. Thome3Alireza Faridar4Jinghong Wang5Shixiang Wen6Loren Ornelas7Dhruv Sareen8Helen S. Goodridge9Clive N. Svendsen10Stanley H. Appel11Department of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX 77030, USADepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX 77030, USADepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX 77030, USADepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX 77030, USADepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX 77030, USADepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX 77030, USADepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX 77030, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Cedars-Sinai Biomanufacturing Center, West Hollywood, CA 90069, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Cedars-Sinai Biomanufacturing Center, West Hollywood, CA 90069, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, 6560 Fannin Street, Suite ST-802, Houston, TX 77030, USA; Corresponding authorSummary: Amyotrophic lateral sclerosis (ALS) is a disorder with immune alterations that augment disease severity. M2 macrophages benefit diabetic and nephrotic mice by suppressing the pro-inflammatory state. However, neither have M2 cells been investigated in ALS nor have human induced pluripotent stem cell (iPSC)-derived M2 cells been thoroughly studied for immunosuppressive potentials. Here, iPSCs of C9orf72 mutated or sporadic ALS patients were differentiated into M2 macrophages, which suppressed activation of pro-inflammatory M1 macrophages as well as proliferation of ALS CD4+CD25- Tc (Teffs). M2 cells converted ALS Teffs into CD4+CD25+Foxp3+ regulatory T cells (Tregs) and rescued Tregs of ALS patients from losing CD25 and Foxp3. Furthermore, Tregs induced or rescued by iPSC-derived M2 had strong suppressive functions. ALS iPSC-derived M2 cells including those with C9orf72 mutation had similar immunomodulatory activity as control iPSC-derived M2 cells. This study demonstrates that M2 cells differentiated from iPSCs of ALS patients are immunosuppressive, boost ALS Tregs, and may serve as a candidate for immune-cell-based therapy to mitigate inflammation in ALS.http://www.sciencedirect.com/science/article/pii/S2589004220303771Cellular NeuroscienceImmunology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Weihua Zhao David R. Beers Jason R. Thonhoff Aaron D. Thome Alireza Faridar Jinghong Wang Shixiang Wen Loren Ornelas Dhruv Sareen Helen S. Goodridge Clive N. Svendsen Stanley H. Appel |
spellingShingle |
Weihua Zhao David R. Beers Jason R. Thonhoff Aaron D. Thome Alireza Faridar Jinghong Wang Shixiang Wen Loren Ornelas Dhruv Sareen Helen S. Goodridge Clive N. Svendsen Stanley H. Appel Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls iScience Cellular Neuroscience Immunology |
author_facet |
Weihua Zhao David R. Beers Jason R. Thonhoff Aaron D. Thome Alireza Faridar Jinghong Wang Shixiang Wen Loren Ornelas Dhruv Sareen Helen S. Goodridge Clive N. Svendsen Stanley H. Appel |
author_sort |
Weihua Zhao |
title |
Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls |
title_short |
Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls |
title_full |
Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls |
title_fullStr |
Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls |
title_full_unstemmed |
Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls |
title_sort |
immunosuppressive functions of m2 macrophages derived from ipscs of patients with als and healthy controls |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2020-06-01 |
description |
Summary: Amyotrophic lateral sclerosis (ALS) is a disorder with immune alterations that augment disease severity. M2 macrophages benefit diabetic and nephrotic mice by suppressing the pro-inflammatory state. However, neither have M2 cells been investigated in ALS nor have human induced pluripotent stem cell (iPSC)-derived M2 cells been thoroughly studied for immunosuppressive potentials. Here, iPSCs of C9orf72 mutated or sporadic ALS patients were differentiated into M2 macrophages, which suppressed activation of pro-inflammatory M1 macrophages as well as proliferation of ALS CD4+CD25- Tc (Teffs). M2 cells converted ALS Teffs into CD4+CD25+Foxp3+ regulatory T cells (Tregs) and rescued Tregs of ALS patients from losing CD25 and Foxp3. Furthermore, Tregs induced or rescued by iPSC-derived M2 had strong suppressive functions. ALS iPSC-derived M2 cells including those with C9orf72 mutation had similar immunomodulatory activity as control iPSC-derived M2 cells. This study demonstrates that M2 cells differentiated from iPSCs of ALS patients are immunosuppressive, boost ALS Tregs, and may serve as a candidate for immune-cell-based therapy to mitigate inflammation in ALS. |
topic |
Cellular Neuroscience Immunology |
url |
http://www.sciencedirect.com/science/article/pii/S2589004220303771 |
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