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Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.

Liu, Yawei LU ; Teige, Ingrid LU ; Birnir, Bryndis LU and Issazadeh, Shohreh LU (2006) In Nature Medicine 12(5). p.518-525
Abstract
Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1–TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+TGF-beta1+CTLA-4+FoxP3+ T regulatory (Treg) cells that suppress... (More)
Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1–TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+TGF-beta1+CTLA-4+FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of TGF-beta1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation. (Less)
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publication status
published
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Nature Medicine
volume
12
issue
5
pages
518 - 525
publisher
Nature Publishing Group
external identifiers
  • wos:000238149100035
  • pmid:16633347
  • scopus:33646596928
ISSN
1546-170X
DOI
10.1038/nm1402
language
English
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yes
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The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuroinflammation (013210006), Department of Clinical Sciences, Malmö (013240000), GABA Channels in Physiology and Pharmacology (013241570), Immunology (013212020)
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d63c814c-a6a2-4ba6-8b60-535b2fb6a60f (old id 155789)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16633347&dopt=Abstract
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2016-04-01 16:53:42
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2020-09-16 02:43:04
@article{d63c814c-a6a2-4ba6-8b60-535b2fb6a60f,
  abstract     = {Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1–TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+TGF-beta1+CTLA-4+FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of TGF-beta1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation.},
  author       = {Liu, Yawei and Teige, Ingrid and Birnir, Bryndis and Issazadeh, Shohreh},
  issn         = {1546-170X},
  language     = {eng},
  number       = {5},
  pages        = {518--525},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.},
  url          = {http://dx.doi.org/10.1038/nm1402},
  doi          = {10.1038/nm1402},
  volume       = {12},
  year         = {2006},
}