Unknown,Transcriptomics,Genomics,Proteomics

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Expression data of hepatic iNKT cells from pLck-hCD1d transgenic mice


ABSTRACT: CD1d expression by thymocytes is required to select iNKT cells. When CD1d is expressed only on thymocytes (pLck-CD1d tg mice), iNKT cells are hyperresponsive to antigen stimulation suggesting that, in physiological conditions, these cells undergo functional education mediated by additional CD1d-expressing cells. Here, we investigated the mechanisms of this functional education. We find that peripheral iNKT cells from pLck-CD1d tg mice express significantly less SHP-1, a tyrosine phosphatase negatively regulating TCR signaling, than WT cells. iNKT cells from heterozygous SHP-1-mutated motheaten mice, displaying similar SHP-1 reduction as pLck-CD1d tg iNKT cells, are antigen-hyperresponsive. Restoring normal CD1d expression in pLck-CD1d tg mice normalizes SHP-1 expression and responsiveness of iNKT cells. In WT mice, iNKT cells upregulate SHP-1 and decrease responsiveness upon emigration from thymus to periphery. This depends on contacts with CD1d-expressing DCs. iNKT cell functional education is therefore controlled by DCs via tuning SHP-1 expression level in the periphery. Hepatic iNKT cells from wild-type and transgenic mice (expressing hCD1d molecule under the pLck promoter)

ORGANISM(S): Mus musculus

SUBMITTER: Giulia Casorati 

PROVIDER: E-GEOD-42835 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Functional education of invariant NKT cells by dendritic cell tuning of SHP-1.

Napolitano Anna A   Pittoni Paola P   Beaudoin Lucie L   Lehuen Agnes A   Voehringer David D   MacDonald H Robson HR   Dellabona Paolo P   Casorati Giulia G  

Journal of immunology (Baltimore, Md. : 1950) 20130220 7


Invariant NKT (iNKT) cells play key roles in host defense by recognizing lipid Ags presented by CD1d. iNKT cells are activated by bacterial-derived lipids and are also strongly autoreactive toward self-lipids. iNKT cell responsiveness must be regulated to maintain effective host defense while preventing uncontrolled stimulation and potential autoimmunity. CD1d-expressing thymocytes support iNKT cell development, but thymocyte-restricted expression of CD1d gives rise to Ag hyperresponsive iNKT ce  ...[more]

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