Regulatory B cells in experimental stroke

Hilary A. Seifert, Arthur Vandenbark, Halina Offner

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Current treatment options for human stroke are limited mainly to the modestly effective infusion of tissue plasminogen activator (tPA), with additional improvement of functional independence and higher rates of angiographic revascularization observed after mechanical thrombectomy. However, new therapeutic strategies that address post-stroke immune-mediated inflammatory responses are urgently needed. Recent studies in experimental stroke have firmly implicated immune mechanisms in the propagation and partial resolution of central nervous system damage after the ischaemic event. A new-found anti-inflammatory role for regulatory B (Breg) cells in autoimmune diseases sparked interest in these cells as potential immunomodulators in stroke. Subsequent studies identified interleukin-10 as a common regulatory cytokine among all five of the currently recognized Breg cell subsets, several of which can be found in the affected brain hemisphere after induction of experimental stroke in mice. Transfer of enriched Breg cell subpopulations into both B-cell-depleted and wild-type mice confirmed their potent immunosuppressive activities in vivo, including recruitment and potentiation of regulatory T cells. Moreover, Breg cell therapy strongly reduced stroke volumes and treatment outcomes in ischaemic mice even when administered 24 hr after induction of experimental stroke, a treatment window far exceeding that of tPA. These striking results suggest that transfer of enriched Breg cell populations could have therapeutic value in human stroke, although considerable clinical challenges remain.

Original languageEnglish (US)
JournalImmunology
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • B cells
  • Brain
  • Cell therapy
  • Neuroinflammation
  • Regulation/suppression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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