n ‐Butyrate downregulates the stimulatory function of peripheral blood‐derived antigen‐presenting cells: a potential mechanism for modulating T‐cell responses by short‐chain fatty acids

n ‐Butyrate downregulates the stimulatory function of peripheral blood‐derived... Modulation of proliferative T‐cell responses by n‐butyrate has been suggested to result from direct interference with cell cycle progression. Considering the important role of antigen‐presenting cells (APC) in T‐cell activation, we were particularly interested in studying the impact of n‐butyrate on these cells. We demonstrated that pretreatment of human peripheral blood mononuclear cells (PBMC) or monocytes with this agent resulted in a dose‐ and time‐dependent downregulation of their capability to stimulate T‐cell responses with a similar pattern of inhibition when this agent was present throughout the culture period. Pretreatment with n‐butyrate was effective in preventing both alloresponses and T‐cell proliferation to immobilized anti‐CD3 monoclonal antibody (mAb) suggesting alteration of costimulatory function. Flow cytometric analysis revealed that interferon‐े (IFN‐े)‐induced upregulation of B7‐1 expression on monocytes was profoundly inhibited by n‐butyrate. Furthermore, this agent significantly suppressed the expression of intercellular adhesion molecule‐1 (ICAM‐1) or lymphocyte function‐associated antigen‐3 (LFA‐3). In contrast, constitutive as well as cytokine‐induced expression of B7‐2 was enhanced by n‐butyrate. Additionally, in monocytes, but not in T cells, treatment with n‐butyrate led to significant alteration of membrane integrity owing to apoptotic cell death. Our findings indicate that modulation of T‐cell responses by n‐butyrate could also result from altered APC function, possibly as a consequence of downregulating distinct adhesion and/or costimulatory receptors as well as of inducing apoptosis. A potential clinical relevance of short‐chain fatty acids for reducing T‐cell‐mediated immune reactions via modulating APC function is speculated. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Immunology Wiley

n ‐Butyrate downregulates the stimulatory function of peripheral blood‐derived antigen‐presenting cells: a potential mechanism for modulating T‐cell responses by short‐chain fatty acids

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Publisher
Wiley
Copyright
Copyright © 1997 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0019-2805
eISSN
1365-2567
DOI
10.1046/j.1365-2567.1997.00337.x
Publisher site
See Article on Publisher Site

Abstract

Modulation of proliferative T‐cell responses by n‐butyrate has been suggested to result from direct interference with cell cycle progression. Considering the important role of antigen‐presenting cells (APC) in T‐cell activation, we were particularly interested in studying the impact of n‐butyrate on these cells. We demonstrated that pretreatment of human peripheral blood mononuclear cells (PBMC) or monocytes with this agent resulted in a dose‐ and time‐dependent downregulation of their capability to stimulate T‐cell responses with a similar pattern of inhibition when this agent was present throughout the culture period. Pretreatment with n‐butyrate was effective in preventing both alloresponses and T‐cell proliferation to immobilized anti‐CD3 monoclonal antibody (mAb) suggesting alteration of costimulatory function. Flow cytometric analysis revealed that interferon‐े (IFN‐े)‐induced upregulation of B7‐1 expression on monocytes was profoundly inhibited by n‐butyrate. Furthermore, this agent significantly suppressed the expression of intercellular adhesion molecule‐1 (ICAM‐1) or lymphocyte function‐associated antigen‐3 (LFA‐3). In contrast, constitutive as well as cytokine‐induced expression of B7‐2 was enhanced by n‐butyrate. Additionally, in monocytes, but not in T cells, treatment with n‐butyrate led to significant alteration of membrane integrity owing to apoptotic cell death. Our findings indicate that modulation of T‐cell responses by n‐butyrate could also result from altered APC function, possibly as a consequence of downregulating distinct adhesion and/or costimulatory receptors as well as of inducing apoptosis. A potential clinical relevance of short‐chain fatty acids for reducing T‐cell‐mediated immune reactions via modulating APC function is speculated.

Journal

ImmunologyWiley

Published: Oct 1, 1997

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