CovidV1, Main, Exploration, bibRecord, 000B56

Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age

Identifieur interne : 000B56 ( Main/Exploration ); précédent : 000B55; suivant : 000B57

Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age

Auteurs : Mingcan Yu ; Guangjin Li ; Won-Woo Lee [Corée du Sud] ; Ming Yuan ; Dapeng Cui ; Cornelia M. Weyand ; Jörg J. Goronzy

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2012.

RBID : PMC:3326453

Abstract

T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both P < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all P < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription (P = 0.002), which inversely correlated with the expression of CD40L (r = 0.65, P = 0.002), ICOS (r = 0.57, P = 0.008), and IL-4 (r = 0.66, P = 0.001). In CD4 KO mice reconstituted with DUSP4 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells (P = 0.003) and the production of ova-specific antibodies (P = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L (P < 0.001), IL-4 (P = 0.007), and IL-21 (P = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly (P = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326453

DOI: 10.1073/pnas.1109797109
PubMed: 22434910
PubMed Central: 3326453

Affiliations:

Corée du Sud

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p>T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both <italic>P</italic>
 < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all <italic>P</italic>
 < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription (<italic>P</italic>
 = 0.002), which inversely correlated with the expression of CD40L (<italic>r</italic>
 = 0.65, <italic>P</italic>
 = 0.002), ICOS (<italic>r</italic>
 = 0.57, <italic>P</italic>
 = 0.008), and IL-4 (<italic>r</italic>
 = 0.66, <italic>P</italic>
 = 0.001). In CD4 KO mice reconstituted with <italic>DUSP4</italic>
 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells (<italic>P</italic>
 = 0.003) and the production of ova-specific antibodies (<italic>P</italic>
 = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L (<italic>P</italic>
 < 0.001), IL-4 (<italic>P</italic>
 = 0.007), and IL-21 (<italic>P</italic>
 = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly (<italic>P</italic>
 = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.</p>
</div>
</front>
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<name sortKey="Li, Guangjin" sort="Li, Guangjin" uniqKey="Li G" first="Guangjin" last="Li">Guangjin Li</name>
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<name sortKey="Yu, Mingcan" sort="Yu, Mingcan" uniqKey="Yu M" first="Mingcan" last="Yu">Mingcan Yu</name>
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Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age

Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age

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