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

Liu, YaweiLund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups (author)

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.

Teige, IngridLund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups(Swepub:lu)infl-ite (author)
Birnir, BryndisLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Institute for Experimental Medical Science, University of Lund,Neuroinflammation Unit(Swepub:uu)brybi979 (author)
Issazadeh, ShohrehLund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)infl-sis (author)
NeuroinflammationForskargrupper vid Lunds universitet (creator_code:org_t)

In:Nature Medicine: Springer Science and Business Media LLC12:5, s. 518-5251546-170X1078-8956

By the author/editor: Liu, Yawei; Teige, Ingrid; Birnir, Bryndis; Issazadeh, Shohr ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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