Intestinal infections establish antigen-specific, long-lived memory CD4⁺ T cells in the brain and meninges.

Authors

Aaron Fleming, Karen Neish, Rafael Di Marco-Barros, David A Posner, Colin Y C Lee, Andrew Stewart, Zewen Kelvin Tuong, Miles Bremridge, Ana Peñalver, Mia Cabantous, Nathan Richoz, Anais Portet, Katherine Harcourt, Eleanor Gillman, Tammie Tao Min Sow, Tetsuo Hasegawa, David Ruano-Gallego, Gad Frankel, David Withers, Simon Clare, Menna R Clatworthy

Published in

Nature neuroscience. Sep 08, 2026. Epub Sep 08, 2026.

Abstract

The meninges form the border between the brain and periphery and house a rich network of immune cells. Here we show that gastrointestinal challenges (intracellular or extracellular bacteria and parasites) reshape the nature of CD4⁺ T cells in the dura mater, the outer meningeal layer, changing the dominant polarization states to T helper (T_H) 1, T_H17 and T_H2 cells, respectively, with differing cytokine profiles. This occurs via CXCR6-CXCL16-dependent migration of gut-activated CD4⁺ T cells to the central nervous system, where they establish long-lived memory populations around the dural venous sinuses, within dural lymphoid aggregates and in the brain. Functionally, these orally primed dural CD4⁺ T were capable of rapid, antigen-specific recall responses, proliferating and producing cytokines upon intravenous rechallenge. Our findings reveal a direct link between intestinal and dural immunity, enabling the central nervous system borders to acquire immunological memory of gut microorganisms, a major source of bloodborne pathogens capable of reaching the brain via fenestrated dural vasculature.

PMID:
42711430
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.