A dominant insulin-specific and islet-destructive T-cell response is sufficient to activate CD8 T cells directed against the fatty-acid receptor GPR40

Spyrantis, Andreas; Krieger, Jana; Stifter, Katja; Boehm, Bernhard O.; Schirmbeck, Reinhold

doi:10.1038/s41423-019-0309-y

Cited by 1 publication

(1 citation statement)

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“…These findings are in line with several recent evidence on the role of omega-3 PUFAs like DHA and EPA in modulating T cell functions in vitro or in vivo [ 35 , 36 , 37 ] as well as following dietary supplementation [ 20 , 38 , 39 , 40 ]. Although we cannot define the mechanism by which DHA deficiency impacts T cell responses in this study, it is plausible that the purported DHA receptors GPR40, GPR120 and PPAR-γ are involved, given that these receptors have recently been associated to Th functions [ 41 , 42 , 43 , 44 ]. Notably, since DHA can be quickly metabolized into the specialized pro-resolving mediators (i.e., resolvins, protectins, and maresins), whose role has been recently reported by our group to potently blunt CTLs and Th1 and Th17 cells [ 15 , 45 , 46 ], this might be an additional possible mechanism for our observed effects in DHA-deficient mice.…”

Section: Discussionmentioning

confidence: 97%

Impairment of Endogenous Synthesis of Omega-3 DHA Exacerbates T-Cell Inflammatory Responses

Talamonti

Jacobsson

Chiurchiù

2023

IJMS

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Omega-3 (ω-3) polyunsaturated fatty acids, including docosahexaenoic acid (DHA), are involved in numerous biological processes and have a range of health benefits. DHA is obtained through the action of elongases (ELOVLs) and desaturases, among which Elovl2 is the key enzyme involved in its synthesis, and can be further metabolized into several mediators that regulate the resolution of inflammation. Our group has recently reported that ELOVL2 deficient mice (Elovl2−/−) not only display reduced DHA levels in several tissues, but they also have higher pro-inflammatory responses in the brain, including the activation of innate immune cells such as macrophages. However, whether impaired synthesis of DHA affects cells of adaptive immunity, i.e., T lymphocytes, is unexplored. Here we show that Elovl2−/− mice have significantly higher lymphocytes in peripheral blood and that both CD8+ and CD4+ T cell subsets produce greater amounts of pro-inflammatory cytokines in both blood and spleen compared to wild type mice, with a higher percentage of cytotoxic CD8+ T cells (CTLs) as well as IFN-γ-producing Th1 and IL-17-producing Th17 CD4+ cells. Furthermore, we also found that DHA deficiency impacts the cross-talk between dendritic cells (DC) and T cells, inasmuch as mature DCs of Elovl2−/− mice bear higher expression of activation markers (CD80, CD86 and MHC-II) and enhance the polarization of Th1 and Th17 cells. Reintroducing DHA back into the diets of Elovl2−/− mice reversed the exacerbated immune responses observed in T cells. Hence, impairment of endogenous synthesis of DHA exacerbates T cell inflammatory responses, accounting for an important role of DHA in regulating adaptive immunity and in potentially counteracting T-cell-mediated chronic inflammation or autoimmunity.

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