IL-2/IL-2R Antibody Complex Enhances Treg-Induced Neuroprotection by Dampening TNF-α Inflammation in an In Vitro Stroke Model

Autor: Bella Gonzales-Portillo, Alma R. Lezama Toledo, Madeline Saft, Jea Y Lee, German Rivera Monroy, Zhen-Jie Wang, Nadia Sadanandan, Mia C Borlongan, Blaise Cozene, Chase Kingsbury, Felipe Esparza Salazar, Alexa Moscatello
Rok vydání: 2021
Předmět:
Zdroj: Neuromolecular Medicine
ISSN: 1559-1174
1535-1084
DOI: 10.1007/s12017-021-08656-0
Popis: The present in vitro study showed that IL-2/IL-2R antibody complex facilitates Treg-induced neuroprotection in the oxygen glucose deprivation/reoxygenation (OGD/R) model of stroke. First, we examined the role of IL-2/IL-2R-treated Tregs in OGD/R-exposed rat primary cortical cells (PCCs), which represent the cell type of the ischemic gray matter in the stroke brain. Here, OGD/R induced cell death, which was attenuated by Tregs and more robustly by IL-2/IL-2R-treated Tregs, but not by IL-2/IL-2R treatment alone. Second, we next assessed IL-2/IL-2R effects in OGD/R-exposed human oligodendrocyte progenitor cells (OPCs), which correspond to the white matter injury after stroke. Results revealed that a similar pattern neuroprotection as seen in the gray matter, in that OGD/R triggered cell death, which was ameliorated by Tregs and more effectively by IL-2/IL-2R-treated Tregs, but IL-2/IL-2R treatment alone was not therapeutic. Third, as we begin to understand the mechanism underlying IL-2/IL-2R engagement of Tregs, we investigated the inflammatory response in OGD/R-exposed human neural progenitor cells (NPCs), which recapitulate both ischemic gray and white matter damage in stroke. Similar to PCCs and OPCs, OGD/R produced cell death and was blocked by Tregs and more efficiently by IL-2/IL-2R-treated Tregs, whereas IL-2/IL-2R treatment alone did not alter the ischemic insult. Moreover, the inflammatory marker, TNF-α, was upregulated after OGD/R, dampened by both Tregs and more efficiently by IL-2/IL-2R-treated Tregs but more pronounced in the latter, and not affected by IL-2/IL-2R treatment alone, suggesting IL-2/IL-2R-Treg-mediated modulation of inflammatory response in stroke. Altogether, these observations support the use of IL-2/IL-2R treatment in enhancing the anti-inflammatory effects of Tregs in stroke.
Databáze: OpenAIRE
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