Sex differences in regulatory cells in experimental stroke

Hilary A. Seifert; Gil Benedek; Jian Liang; Ha Nguyen; Gail Kent; Arthur A. Vandenbark; Julie A. Saugstad; Halina Offner

doi:10.1016/j.cellimm.2017.06.003

Sex differences in regulatory cells in experimental stroke

Hilary A. Seifert
, Gil Benedek
, Jian Liang
, Ha Nguyen
, Gail Kent
, Arthur A. Vandenbark
, Julie A. Saugstad
, Halina Offner

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19⁺CD5⁺CD1d^hi B10 cells as well as anti-inflammatory CD11b⁺CD206⁺ microglia/macrophages in the ipsilateral vs. contralateral hemisphere of female but not male mice undergoing 60 min middle cerebral artery occlusion followed by 96 h of reperfusion. Moreover, female mice with MCAO had increased total spleen cell numbers but lower B10 levels in spleens. These results elucidate differing sex-dependent regulatory mechanisms that account for diminished stroke severity in females and underscore the need to test immune-modulating therapies for stroke in both males and females.

Original language	English (US)
Pages (from-to)	49-54
Number of pages	6
Journal	Cellular Immunology
Volume	318
DOIs	https://doi.org/10.1016/j.cellimm.2017.06.003
State	Published - Aug 2017

Funding

This work was supported by NIH/National Institute of Neurological Disorders and Stroke 1RO1 NS075887 (H.O.) and 1RO1 NS076013 (H.O., J.S.) and the American Heart Association 17GRNT33220001 (H.O). This material is the result of work supported, in part, with resources and the use of facilities at the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. This work was supported by NIH/National Institute of Neurological Disorders and Stroke 1RO1 NS075887 (H.O.) and 1RO1 NS076013 (H.O., J.S.) and the American Heart Association 17GRNT33220001 (H.O). This material is the result of work supported, in part, with resources and the use of facilities at the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Funders	Funder number
American Heart Association 17GRNT33220001	17GRNT33220001
NIH/National Institute of Neurological Disorders and Stroke 1RO1 NS075887	1RO1 NS076013, 1RO1 NS075887
United States Government
Veterans Health Administration
National Institute of Neurological Disorders and Stroke	R01NS075887
U.S. Department of Veterans Affairs
Office of Research and Development Clinical Research and Development Program
Biomedical Laboratory Research and Development, VA Office of Research and Development

Keywords

Anti-inflammatory macrophages
Lymphocyte
Middle cerebral artery occlusion
Regulatory B cells
Regulatory T cells
Sex-specific

ASJC Scopus subject areas

Immunology

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10.1016/j.cellimm.2017.06.003

Cite this

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title = "Sex differences in regulatory cells in experimental stroke",

abstract = "Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19+CD5+CD1dhi B10 cells as well as anti-inflammatory CD11b+CD206+ microglia/macrophages in the ipsilateral vs. contralateral hemisphere of female but not male mice undergoing 60 min middle cerebral artery occlusion followed by 96 h of reperfusion. Moreover, female mice with MCAO had increased total spleen cell numbers but lower B10 levels in spleens. These results elucidate differing sex-dependent regulatory mechanisms that account for diminished stroke severity in females and underscore the need to test immune-modulating therapies for stroke in both males and females.",

keywords = "Anti-inflammatory macrophages, Lymphocyte, Middle cerebral artery occlusion, Regulatory B cells, Regulatory T cells, Sex-specific",

author = "Seifert, \{Hilary A.\} and Gil Benedek and Jian Liang and Ha Nguyen and Gail Kent and Vandenbark, \{Arthur A.\} and Saugstad, \{Julie A.\} and Halina Offner",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = aug,

doi = "10.1016/j.cellimm.2017.06.003",

language = "English (US)",

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AU - Seifert, Hilary A.

AU - Benedek, Gil

AU - Liang, Jian

AU - Nguyen, Ha

AU - Kent, Gail

AU - Vandenbark, Arthur A.

AU - Saugstad, Julie A.

AU - Offner, Halina

PY - 2017/8

Y1 - 2017/8

N2 - Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19+CD5+CD1dhi B10 cells as well as anti-inflammatory CD11b+CD206+ microglia/macrophages in the ipsilateral vs. contralateral hemisphere of female but not male mice undergoing 60 min middle cerebral artery occlusion followed by 96 h of reperfusion. Moreover, female mice with MCAO had increased total spleen cell numbers but lower B10 levels in spleens. These results elucidate differing sex-dependent regulatory mechanisms that account for diminished stroke severity in females and underscore the need to test immune-modulating therapies for stroke in both males and females.

AB - Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19+CD5+CD1dhi B10 cells as well as anti-inflammatory CD11b+CD206+ microglia/macrophages in the ipsilateral vs. contralateral hemisphere of female but not male mice undergoing 60 min middle cerebral artery occlusion followed by 96 h of reperfusion. Moreover, female mice with MCAO had increased total spleen cell numbers but lower B10 levels in spleens. These results elucidate differing sex-dependent regulatory mechanisms that account for diminished stroke severity in females and underscore the need to test immune-modulating therapies for stroke in both males and females.

KW - Anti-inflammatory macrophages

KW - Lymphocyte

KW - Middle cerebral artery occlusion

KW - Regulatory B cells

KW - Regulatory T cells

KW - Sex-specific

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VL - 318

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EP - 54

JO - Cellular Immunology

JF - Cellular Immunology

ER -

Sex differences in regulatory cells in experimental stroke

Abstract

Funding

Keywords

ASJC Scopus subject areas

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