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IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke

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Abstract

Clinical stroke induces inflammatory processes leading to cerebral injury. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that absence of B-cells led to larger infarct volumes and increased numbers of activated T-cells, monocytes and microglial cells in the brain, thus implicating a regulatory role of B-cell subpopulations in limiting CNS damage from stroke. The aim of this study was to determine whether the IL-10-producing regulatory B-cell subset can limit CNS inflammation and reduce infarct volume following ischemic stroke in B-cell deficient (μMT−/−) mice. Five million IL-10-producing B-cells were obtained from IL-10-GFP reporter mice and transferred i.v. to μMT−/−mice. After 24 h following this transfer, recipients were subjected to 60 min of middle cerebral artery occlusion (MCAO) followed by 48 h of reperfusion. Compared to vehicle-treated controls, the IL-10+ B-cell-replenished μMT−/−mice had reduced infarct volume and fewer infiltrating activated T-cells and monocytes in the affected brain hemisphere. These effects in CNS were accompanied by significant increases in regulatory T-cells and expression of the co-inhibitory receptor, PD-1, with a significant reduction in the proinflammatory milieu in the periphery. These novel observations provide the first proof of both immunoregulatory and protective functions of IL-10-secreting B-cells in MCAO that potentially could impart significant benefit for stroke patients in the clinic.

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Acknowledgements

The authors wish to thank Melissa Barber for assistance with manuscript preparation. This work was supported by NIH/NINDS 1RO1 NS075887. This material is based upon work supported in part by 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 Department of Veterans Affairs or the United States Government.

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. Neuroimmunology Research, VA Medical Center, R&D-31, Portland Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd, Portland, OR, 97239, USA

    Sheetal Bodhankar, Arthur A. Vandenbark & Halina Offner

  2. Department of Neurology, Oregon Health & Science University, Portland, OR, USA

    Sheetal Bodhankar, Arthur A. Vandenbark & Halina Offner

  3. Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA

    Arthur A. Vandenbark

  4. Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA

    Yingxin Chen, Stephanie J. Murphy & Halina Offner

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  1. Sheetal Bodhankar
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  2. Yingxin Chen
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  3. Arthur A. Vandenbark
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  4. Stephanie J. Murphy
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  5. Halina Offner
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Correspondence to Halina Offner.

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Sheetal Bodhankar and Yingxin Chen contributed equally to this work.

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Bodhankar, S., Chen, Y., Vandenbark, A.A. et al. IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke. Metab Brain Dis 28, 375–386 (2013). https://doi.org/10.1007/s11011-013-9413-3

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