Title |
Regulation of learning and memory by meningeal immunity: a key role for IL-4
|
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Published in |
The Journal of Experimental Medicine, May 2010
|
DOI | 10.1084/jem.20091419 |
Pubmed ID | |
Authors |
Noël C. Derecki, Amber N. Cardani, Chun Hui Yang, Kayla M. Quinnies, Anastasia Crihfield, Kevin R. Lynch, Jonathan Kipnis |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 36% |
Singapore | 1 | 9% |
Japan | 1 | 9% |
Unknown | 5 | 45% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 5 | 45% |
Members of the public | 5 | 45% |
Practitioners (doctors, other healthcare professionals) | 1 | 9% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 10 | 2% |
Portugal | 2 | <1% |
South Africa | 2 | <1% |
France | 1 | <1% |
Italy | 1 | <1% |
Netherlands | 1 | <1% |
Iran, Islamic Republic of | 1 | <1% |
Germany | 1 | <1% |
Russia | 1 | <1% |
Other | 1 | <1% |
Unknown | 617 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 138 | 22% |
Researcher | 91 | 14% |
Student > Bachelor | 83 | 13% |
Student > Master | 54 | 8% |
Student > Doctoral Student | 46 | 7% |
Other | 115 | 18% |
Unknown | 111 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 128 | 20% |
Neuroscience | 125 | 20% |
Medicine and Dentistry | 66 | 10% |
Biochemistry, Genetics and Molecular Biology | 59 | 9% |
Immunology and Microbiology | 51 | 8% |
Other | 60 | 9% |
Unknown | 149 | 23% |