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Review
. 2024 Dec;54(12):e2451067.
doi: 10.1002/eji.202451067. Epub 2024 Oct 13.

IL-17A-producing γδ T cells: A novel target in stroke immunotherapy

Marius Piepke  1 , Alina Jander  1 , Nicola Gagliani  2 , Mathias Gelderblom  1
Affiliations
Review

IL-17A-producing γδ T cells: A novel target in stroke immunotherapy

Marius Piepke et al. Eur J Immunol. 2024 Dec.

Abstract

The activation of the immune system is crucial for the fate of the ischemic brain tissue and neurological outcome in experimental stroke. Rapidly after stroke γδ (γδ17), T cells release IL-17A in the ischemic brain and thereby amplify the early detrimental immune response. Notably, IL-17A levels in γδ17 T cells are modulated by the intestinal microbiota which is, in turn, shaped by the diet. Importantly, besides their proinflammatory effects, meningeal γδ17 T cells have been recently implicated in regulating neuronal signaling, behavior, and cognition under homeostatic and pathological conditions at the brain-meningeal interface. Against this background, we propose that a dietary intervention represents a promising treatment option to improve poststroke outcomes by the modulation of the microbiota composition and IL-17A levels in γδ T cells.

Keywords: Interleukin‐17A; Meninges; Microbiota; Stroke; γδ T cells.

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Conflict of interest statement

N.G. declares financial support from F. Hoffmann‐La Roche. This is outside the submitted work. The remaining authors declare no commercial or financial conflict of interest.

Figures

Figure 1
Figure 1
Potential targets for a modulation of γδ17 T cells by a dietary intervention in stroke. Stroke‐induced gut microbiota‐dysbiosis (reduced Bacteroidetes/Firmicutes ratio, reduced α‐diversity, etc.) is associated with an expansion of γδ17 T cells in the intestine and CNS. The authors propose that the alternation of dietary components with a known impact on IL‐17A production in T cells is an opportunity to modulate stroke outcomes. Based on current literature, the proposed dietary interventions can mediate their effects on IL‐17A production in T cells either via (green) [22, 23, 26, 27, 29] or independently from SCFAs (orange) [38, 39, 46].
Figure 2
Figure 2
Meningeal γδ17 T cells in health and disease. γδ17 T cells populate the meninges under homeostatic conditions and modulate higher brain functions through neurons (N), astrocytes (A), microglia (M), and border‐associated macrophages (BAMs) [10, 11, 46]. In stroke, γδ17 T cells rapidly infiltrate the ischemic brain and amplify the inflammatory response by inducing neutrophil‐attracting CXC‐chemokines [5, 6].
See this image and copyright information in PMC

References

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