Immunosuppressive Functions of M2 Macrophages Derived from iPSCs of Patients with ALS and Healthy Controls

IScience
Weihua ZhaoStanley H Appel

Abstract

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.

Citations

Apr 24, 2021·Neuroscience Letters·Laura Ferraiuolo, Nicholas J Maragakis
May 1, 2021·Nature Reviews. Neurology·Björn F VahsenMartin R Turner
Jul 28, 2021·Free Radical Biology & Medicine·J Jiménez-VillegasA I Rojo
Jul 30, 2021·Cellular and Molecular Life Sciences : CMLS·Francesco LiguoriCinzia Volonté
Aug 8, 2021·International Journal of Molecular Sciences·Sourav PanjaBibhash C Paria
Aug 26, 2021·Journal of Extracellular Vesicles·Amin ZakeriPeter Nejsum

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Methods Mentioned

BETA
transgenic
flow cytometry
ELISA

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