The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia

Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator...

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Main Authors:	Koh, Han Seok, Chang, Chi Young, Jeon, Sae-Bom, Yoon, Hee Jung, Ahn, Ye-Hyeon, Kim, Hyung-Seok, Kim, In-Hoo, Jeon, Sung Ho, Johnson, Randall S., Park, Eun Jung
Format:	Online
Language:	English
Published:	Nature Pub. Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383004/

id	pubmed-4383004
recordtype	oai_dc
spelling	pubmed-43830042015-04-07 The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia Koh, Han Seok Chang, Chi Young Jeon, Sae-Bom Yoon, Hee Jung Ahn, Ye-Hyeon Kim, Hyung-Seok Kim, In-Hoo Jeon, Sung Ho Johnson, Randall S. Park, Eun Jung Article Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1α-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1α-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases. Nature Pub. Group 2015-03-20 /pmc/articles/PMC4383004/ /pubmed/25790768 http://dx.doi.org/10.1038/ncomms7340 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Koh, Han Seok Chang, Chi Young Jeon, Sae-Bom Yoon, Hee Jung Ahn, Ye-Hyeon Kim, Hyung-Seok Kim, In-Hoo Jeon, Sung Ho Johnson, Randall S. Park, Eun Jung
spellingShingle	Koh, Han Seok Chang, Chi Young Jeon, Sae-Bom Yoon, Hee Jung Ahn, Ye-Hyeon Kim, Hyung-Seok Kim, In-Hoo Jeon, Sung Ho Johnson, Randall S. Park, Eun Jung The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia
author_facet	Koh, Han Seok Chang, Chi Young Jeon, Sae-Bom Yoon, Hee Jung Ahn, Ye-Hyeon Kim, Hyung-Seok Kim, In-Hoo Jeon, Sung Ho Johnson, Randall S. Park, Eun Jung
author_sort	Koh, Han Seok
title	The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia
title_short	The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia
title_full	The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia
title_fullStr	The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia
title_full_unstemmed	The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia
title_sort	hif-1/glial tim-3 axis controls inflammation-associated brain damage under hypoxia
description	Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1α-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1α-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases.
publisher	Nature Pub. Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383004/
_version_	1613206729827287040

The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia

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