Regulation of learning and memory by meningeal immunity: a key role for IL-4.
J Exp Med
; 207(5): 1067-80, 2010 May 10.
Article
in En
| MEDLINE
| ID: mdl-20439540
ABSTRACT
Proinflammatory cytokines have been shown to impair cognition; consequently, immune activity in the central nervous system was considered detrimental to cognitive function. Unexpectedly, however, T cells were recently shown to support learning and memory, though the underlying mechanism was unclear. We show that one of the steps in the cascade of T cell-based support of learning and memory takes place in the meningeal spaces. Performance of cognitive tasks led to accumulation of IL-4-producing T cells in the meninges. Depletion of T cells from meningeal spaces skewed meningeal myeloid cells toward a proinflammatory phenotype. T cell-derived IL-4 was critical, as IL-4(-/-) mice exhibited a skewed proinflammatory meningeal myeloid cell phenotype and cognitive deficits. Transplantation of IL-4(-/-) bone marrow into irradiated wild-type recipients also resulted in cognitive impairment and proinflammatory skew. Moreover, adoptive transfer of T cells from wild-type into IL-4(-/-) mice reversed cognitive impairment and attenuated the proinflammatory character of meningeal myeloid cells. Our results point to a critical role for T cell-derived IL-4 in the regulation of cognitive function through meningeal myeloid cell phenotype and brain-derived neurotrophic factor expression. These findings might lead to the development of new immune-based therapies for cognitive impairment associated with immune decline.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interleukin-4
/
Learning
Limits:
Animals
Language:
En
Journal:
J Exp Med
Year:
2010
Document type:
Article
Affiliation country:
United States