n-3 Polyunsaturated Fatty Acids Impede the TCR Mobility and the TCR–pMHC Interaction of Anti-Viral CD8+ T Cells

Abstract

The immune-suppressive effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on T cells have been observed via multiple in vitro and in vivo models. However, the precise mechanism that causes these effects is still undefined. In this study, we investigated whether n-3 PUFAs regulated T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions. The expansion of anti-viral CD8+ T cells that endogenously synthesize n-3 PUFAs (FAT-1) dramatically decreased upon lymphocytic choriomeningitis virus (LCMV) infection in vivo. This decrease was not caused by the considerable reduction of TCR expression or the impaired chemotactic activity of T cells. Interestingly, a highly inclined and laminated optical sheet (HILO) microscopic analysis revealed that the TCR motility was notably reduced on the surface of the FAT-1 CD8+ T cells compared to the wild type (WT) CD8+ T cells. Importantly, the adhesion strength of the FAT-1 CD8+ T cells to the peptide-MHC was significantly lower than that of the WT CD8+T cells. Consistent with this result, treatment with docosahexaenoic acid (DHA), one type of n-3 PUFA, significantly decreased CD8+ T cell adhesion to the pMHC. Collectively, our results reveal a novel mechanism through which n-3 PUFAs decrease TCR-pMHC interactions by modulating TCR mobility on CD8+ T cell surfaces.

Alpha-Linolenic Acid Modulates T Cell Incorporation in a 3D Tissue-Engineered Psoriatic Skin Model

“…Additionally, CD3-labeled T cells were present only in the dermal compartment of PS +T+ALA , confirming that the addition of ALA to the culture medium decreased the migration of T cells towards the dermo-epidermal junction. A recent study revealed that the percentage of CD45+ cells among CD8+ T cells was decreased in FAT-1 mice, which are capable of producing n-3 PUFAs independently [53]. The decreased expression of ICAM-1 in PS +T+ALA also confirms that ALA minimizes the ability of T cells to bind to keratinocytes in the psoriatic substitutes.…”

Special Issue “Viral Evasion or Suppression of Host Immunity”

“…This could be a potential pathogenetic mechanism for the loss of T lymphocytes which has been observed during SRV infection. Interestingly, Lim et al demonstrated that omega-3 ( n -3) polyunsaturated fatty acids (PUFAs) interfere with MHC-TCR interactions in CD8 + T cells [ 6 ]. In this study, highly inclined and laminated optical sheet microscopic analysis was used to uncover how TCR motility was reduced on the anti-viral CD8 + T cells that endogenously synthesize n -3 PUFAs.…”