Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection

Saame Raza Shaikh, Michael A Edidin

Research output: Contribution to journalArticle

Abstract

Polyunsaturated fatty acids (PUFAs), notably of the n-3 series, have immunosuppressive effects which make these molecules candidates for treating inflammatory symptoms associated with cardiovascular disease, obesity, arthritis, and asthma. However, immunosuppression by PUFAs could increase susceptibility to bacterial and viral infection. A detailed molecular picture is required in order to understand the balance between the benefits and risks of utilizing PUFAs as adjuvant immunosuppressants. Here we review evidence that incorporation of PUFAs into membrane lipids of antigen presenting cells (APCs) downregulates APC function. We propose that PUFAs modulate antigen presentation by altering the organization of lipid and protein molecules of the plasma membrane and endomembranes; this alters recognition and responses by T cells. The foundation of our hypothesis is built on data from artificial bilayer experiments which provide the physical principles by which PUFA acyl chains affect membrane architecture. This review also reconciles conflicting results in the literature by discussing the advantages and disadvantages of differing methods of PUFA treatment of cells. We suggest that membrane modulation of immune cells may be an important and overlooked mechanism of immunomodulation. In addition, we propose that mechanistic studies with defined experimental protocols will speed the translation of laboratory studies on PUFAs to the clinic.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalChemistry and Physics of Lipids
Volume153
Issue number1
DOIs
StatePublished - May 2008

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Unsaturated Fatty Acids
Immunotherapy
Membranes
Infection
Antigen-Presenting Cells
Immunosuppressive Agents
Molecules
T-cells
Immunomodulation
Omega-3 Fatty Acids
Antigen Presentation
Virus Diseases
Cell membranes
Membrane Lipids
Bacterial Infections
Immunosuppression
Arthritis
Cardiovascular Diseases
Down-Regulation
Asthma

Keywords

  • Antigen presentation
  • Major histocompatibility complex
  • Membrane structure
  • Polyunsaturated fatty acids

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

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AB - Polyunsaturated fatty acids (PUFAs), notably of the n-3 series, have immunosuppressive effects which make these molecules candidates for treating inflammatory symptoms associated with cardiovascular disease, obesity, arthritis, and asthma. However, immunosuppression by PUFAs could increase susceptibility to bacterial and viral infection. A detailed molecular picture is required in order to understand the balance between the benefits and risks of utilizing PUFAs as adjuvant immunosuppressants. Here we review evidence that incorporation of PUFAs into membrane lipids of antigen presenting cells (APCs) downregulates APC function. We propose that PUFAs modulate antigen presentation by altering the organization of lipid and protein molecules of the plasma membrane and endomembranes; this alters recognition and responses by T cells. The foundation of our hypothesis is built on data from artificial bilayer experiments which provide the physical principles by which PUFA acyl chains affect membrane architecture. This review also reconciles conflicting results in the literature by discussing the advantages and disadvantages of differing methods of PUFA treatment of cells. We suggest that membrane modulation of immune cells may be an important and overlooked mechanism of immunomodulation. In addition, we propose that mechanistic studies with defined experimental protocols will speed the translation of laboratory studies on PUFAs to the clinic.

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