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A role for the peroxisome proliferator-activated receptor α in T-cell physiology and ageing immunobiology

Published online by Cambridge University Press:  05 March 2007

Dallas C. Jones ,
Bernadette M. Manning  and
Raymond A. Daynes
Dallas C. Jones
Affiliation:
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
Bernadette M. Manning
Affiliation:
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
Raymond A. Daynes*
Affiliation:
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Salt Lake City, Utah 84112, USA
*
*Corresponding author: Dr Raymond A. Daynes, fax + 1 801 581 8946, email [email protected]
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Abstract

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Peroxisome proliferator-activated receptor (PPAR) α represents an important member of the nuclear hormone receptor superfamily that can be activated by a variety of natural fatty acids, some of their metabolites and by commonly-used anti-lipidaemic drugs. We recently demonstrated PPARα expression in T lymphocytes, where it controls the initiation of transcription of T-box expressed in T-cells (T-bet) independent of added agonist. T-bet is an activation-inducible transcription factor regulator of interleukin 2 (suppression) and interferon γ (stimulation) synthesis. A suppressed ability to produce interleukin 2 and an enhanced production of interferon γ occurs in activated T-cells from PPARα-/- mice, as well as in T-cells from wild-type aged animals whose lymphocytes express lowered basal levels of PPARα. The dysregulated expression and/or function of cytokines, glucocorticoids or leptin that occurs with advanced age could all be responsible for the reduced expression of PPARα. Dietary supplementation of aged mice with vitamin E, or supplementation with known agonists of PPARα, was associated with elevation of lymphocyte expression of this nuclear hormone receptor, restoration of control over T-bet expression and elimination of the dysregulated production of interleukin 2 and interferon γ following lymphocyte activation. Interleukin 2 and interferon γ play very important roles in the initiation and/or regulation of immune, inflammatory and autoimmune disease states. Thus, the mechanisms that control the timing, magnitude and duration of specific cytokine production by activated T lymphocytes need clarification before appropriate nutritional or therapeutic strategies can be devised to treat disease conditions where cytokine expression and/or activities are deemed to be dysregulated and responsible.

Keywords

AgeingPPARαImmunobiology
Type
Mechanisms in nutrient regulation of inflammation
Information
Proceedings of the Nutrition Society , Volume 61 , Issue 3 , August 2002 , pp. 363 - 369
Copyright
Copyright © The Nutrition Society 2002

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