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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Dietary fish oil inhibits antigen-specific murine Th1 cell development by suppression of clonal expansion
Ping Zhang1, Wooki Kim, Lan Zhou
1Department of Microbial and Molecular Pathogenesis, Texas A&M University System Health Science Center, College Station, TX, USA.
Abstract:
To determine the mechanisms by which dietary fish oil (FO) affects antigen-stimulated Th1 cell development, DO11.10 Rag 2(-/-) T cell receptor transgenic mice were fed a control diet (5% corn oil (CO) or a FO diet (1% CO + 4% FO, (n-3) PUFA) for 2 wk. CD4(+) T cells were cultured under neutral or Th1 polarizing conditions. FO feeding suppressed (P < 0.05) ovalbumin peptide-induced proliferation of nonpolarized CD4(+) T cells. Differentiation in vitro to Th1 cells was not affected by dietary FO, as evidenced by similar percentages of KJ1-26(+), IFN-gamma(+), IL-4(-) Th1 cells in cultures from CO-fed (99%) and FO-fed (97%) mice. However, the absolute number of viable Th1 cells in polarized cultures from FO-fed mice was less than half that observed in CO-fed mice (P < 0.05), indicating that FO inhibits in vitro Th1 clonal expansion. The reduced number of Th1 cells in FO cultures was not a result of increased apoptosis, because similar percentages of apoptotic Th1 cells were observed in cultures from FO- and CO-fed mice. IL-2-induced cell proliferation was significantly decreased in polarized Th1 cells from the FO group; however, the suppressed proliferation was not linked to reduced CD25 surface expression on antigen-stimulated CD4(+) T cells. Adoptively transferred CFSE-labeled DO11.10 CD4(+) cells into immunized mice (Th1 polarizing agents) showed that dietary FO reduced (P < 0.05) the number of cell divisions in vivo. These studies suggest that the attenuated inflammatory response which accompanies FO feeding may be explained, at least in part, by suppression of Th1 clonal expansion.
Insights
Dietary fish oil (FO) suppresses T helper 1 (Th1) cell clonal expansion and proliferation, reducing inflammatory responses. This occurs without affecting Th1 differentiation or increasing apoptosis, suggesting a key mechanism for FO
Area of Science:
- Immunology
- Nutrition Science
- Molecular Biology
Background:
- Dietary omega-3 polyunsaturated fatty acids (PUFAs), particularly from fish oil (FO), are known to modulate immune responses.
- T helper 1 (Th1) cells play a critical role in cell-mediated immunity and inflammatory processes.
- Understanding the precise mechanisms by which FO influences Th1 cell development is crucial for its therapeutic applications.
Purpose of the Study:
- To investigate the effects of dietary fish oil (FO) on antigen-stimulated Th1 cell development and function.
- To elucidate the mechanisms underlying FO's impact on Th1 cell proliferation and clonal expansion.
- To determine if FO influences Th1 cell differentiation, apoptosis, or interleukin-2 (IL-2) responsiveness.
Main Methods:
- DO11.10 Rag 2(-/-) T cell receptor transgenic mice were fed either a control corn oil (CO) diet or a FO-rich diet for two weeks.
- CD4(+) T cells were isolated and cultured under neutral or Th1 polarizing conditions.
- Ovalbumin peptide-induced proliferation, Th1 cell differentiation (IFN-gamma+, IL-4-), apoptosis, IL-2-induced proliferation, and CD25 surface expression were assessed.
- Adoptive transfer of CFSE-labeled T cells into immunized mice was performed to evaluate in vivo cell division.
Main Results:
- Dietary FO suppressed ovalbumin peptide-induced proliferation of nonpolarized CD4(+) T cells.
- Th1 cell differentiation was not affected by FO feeding, with similar percentages of Th1 cells observed in both groups.
- However, FO feeding significantly reduced the absolute number of viable Th1 cells in polarized cultures, indicating suppressed clonal expansion.
- FO did not increase Th1 cell apoptosis but did decrease IL-2-induced proliferation of polarized Th1 cells.
- In vivo studies confirmed that dietary FO reduced the number of T cell divisions.
Conclusions:
- Dietary fish oil (FO) suppresses Th1 clonal expansion and proliferation, both in vitro and in vivo.
- This suppression of Th1 cell expansion, rather than differentiation or apoptosis, appears to be a key mechanism by which FO attenuates inflammatory responses.
- FO may reduce inflammatory conditions by limiting the magnitude of the Th1 cell-mediated immune response.
