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

Immunology. 1997 Oct;92(2):234-43. doi: 10.1046/j.1365-2567.1997.00337.x.


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-gamma (IFN-gamma)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / drug effects*
  • Antigen-Presenting Cells / immunology
  • Antigens, Surface / metabolism
  • Apoptosis / drug effects
  • Butyrates / pharmacology*
  • Butyric Acid
  • Cell Culture Techniques
  • Down-Regulation / drug effects*
  • Humans
  • Immune Tolerance
  • Lymphocyte Activation / drug effects*
  • Monocytes / drug effects
  • Monocytes / immunology
  • T-Lymphocytes / immunology*
  • Time Factors


  • Antigens, Surface
  • Butyrates
  • Butyric Acid