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

Abstract

Psoriasis is an autoimmune skin disease with an increased number of leukocytes infiltrating the dermal and epidermal compartments compared with normal skin. N-3 polyunsaturated fatty acids (n-3 PUFAs) are frequently used in the clinic in order to attenuate the symptoms of psoriasis. For psoriatic patients, a supplementation of the diet with alpha-linolenic acid (ALA) reduces the activation of T cell signaling pathways, leading to a significant reduction in inflammatory cytokine secretion. However, the precise mechanism of action of n-3 PUFAs in psoriasis is still not understood. In the present study, we elucidated the bioaction of ALA on the adaptive immune component of psoriasis by using a psoriatic skin model produced with the addition of activated T cells. Healthy and psoriatic skin substitutes were produced according to the self-assembly method, using culture media supplemented with 10 μM of ALA. T cells were isolated from blood samples using a negative selection isolation method. ALA supplementation regulated the hyperproliferation and abnormal cell differentiation of psoriatic keratinocytes stimulated by T cells. Additionally, the exogenous ALA was correctly incorporated into the phospholipids of keratinocytes, which resulted in increased levels of ALA, eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA). The infiltration of T cells into the epidermis was reduced when ALA was added to the culture medium, and significant decreases in the levels of inflammatory cytokines and chemokines such as CXCL1, interleukin-6 (IL-6) and interleukin-8 (IL-8) were consequently measured in psoriatic substitutes supplemented with this n-3 PUFA. Altogether, our results showed that in this psoriatic skin model enriched with T cells, ALA exerted its beneficial effect by decreasing the quantities of inflammatory mediators released by T cells.

Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling

“…Although the signalization involved in the pathogenesis of psoriasis has been investigated in recent years, much remains to be discovered. In this regard, our previous studies aimed to investigate the cellular and molecular mechanisms of psoriasis [ 7 , 8 , 10 , 13 , 33 , 34 , 35 , 36 ]. More recently, we developed a more complex biomaterial allowing the study of the interaction between skin and immune cells in a microenvironment that closely mimics that of the pathology [ 4 ].…”

Dietary Ground Flaxseed Increases Serum Alpha-Linolenic Acid Concentrations in Adult Cats

“…Ingredients that supply DHA and EPA n-3 PUFA are often the focus on contributing to the immunomodulatory effects rather than ALA due to cats having low delta-6 desaturase activity and lack of conversion of ALA to DPA and EPA. However, all three n-3 PUFAs play important roles in modulating the immune system through synthesis of prostaglandins and leukotrienes [ 32 ] and decrease inflammatory mediators released by T-cells [ 12 ]. Specifically, improving concentrations of ALA can improve skin moisture retention and result in skin and coat improvements in pets with poor coat quality [ 33 ].…”

“…However, the mechanistic insight into ALA’s anti-inflammatory impact has been demonstrated in vitro by modulating NF-κB and mitogen-activated protein kinase [ 10 , 11 ]. More recently, ALA has been linked to decreasing pro-inflammatory mediators from T-cells, suggesting a direct effect of ALA on suppressing inflammation [ 12 ]. Furthermore, it has been observed that feeding flaxseed oil for 12 weeks to adult cats resulted in increased serum concentrations of ALA [ 13 ].…”

Current knowledge of the implication of lipid mediators in psoriasis

“…Additionally, n-3 PUFAs seem to affect the immune system (34). Indeed, ALA was showed to affect T cell functions in the reconstructed psoriatic skin model, mainly by decreasing the production of inflammatory cytokines (200). The impact of n-3 PUFAs on the adaptive immunity have also been studied in other models.…”