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Impairment of non-muscle myosin IIA in human CD4+ T cells contributes to functional deficits in the elderly.

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Cané, Stefania [UCL] Ponnappan, Subramaniam Ponnappan, Usha

Physiological aging imposes significant alterations in the repertoire of T cells and all associated functions. Although several studies have reported defects upon antigen-induced activation of T cells during aging, the molecular mechanisms that control T-cell receptor (TCR) downmodulation remain to be fully defined. While previous studies have assessed the role of F-actin in regulating activation-induced TCR internalization, few have delineated the roles of motor proteins, such as non-muscle myosin IIA (NMMIIA). In this study, we describe a series of experiments supporting the hypothesis that effective TCR downmodulation requires not only efficient reorganization of the actin cytoskeleton, but also functional NMMIIA. For the first time, we show that CD4(+) T cells from elderly human donors have dysfunctional NMMIIA that contributes to delaying activation-induced TCR internalization and impairing calcium mobilization. Additionally, our results demonstrate that chemical inhibition of NMMIIA in CD4(+) T cells from young donors also results in complete abrogation of TCR internalization, strongly supporting the fundamental role of NMMIIA in modulating this event. Recent observations that the generation of an efficient T-cell response requires migration prompted us to investigate whether NMMIIA also plays a regulatory role in CD4(+) T-cell migration. We show that chemical inhibition of NMMIIA downmodulates chemotactic migration in CD4(+) T cells from both young and elderly donors. Together, these data demonstrate a significant contribution of dysfunctional NMMIIA to TCR-mediated functional defects during aging.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2012
Language Anglais
Journal information "Cellular & Molecular Immunology" - Vol. 9, no.1, p. 86-96 (2012)
Peer reviewed yes
Publisher Chinese Society of Immunology
issn 1672-7681
e-issn 2042-0226
Publication status Publié
Affiliation UCL - SSS/DDUV - Institut de Duve
MESH Subject Adult ; Male ; Nonmuscle Myosin Type IIA ; Receptors, Antigen, T-Cell ; Aged ; Aged, 80 and over ; Aging ; CD4-Positive T-Lymphocytes ; Chemotaxis, Leukocyte ; Cytoskeleton ; Female ; Humans
Links
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Bibliographic reference Cané, Stefania ; Ponnappan, Subramaniam ; Ponnappan, Usha. Impairment of non-muscle myosin IIA in human CD4+ T cells contributes to functional deficits in the elderly.. In: Cellular & Molecular Immunology, Vol. 9, no.1, p. 86-96 (2012)
Permanent URL http://hdl.handle.net/2078.1/138348