Naturally Oxidized Olive Oil Promotes Active Cutaneous Anaphylaxis and Th2 Cytokine Production.

The excessive ingestion of oxidized dietary oils may exacerbate some allergic diseases. We previously reported that oxidized olive oil exacerbates active cutaneous anaphylaxis (ACA), one of the immediate allergic reactions. This study was conducted to clarify the effects of oxidized olive oil on the T cell response during ACA. BALB/c female mice were orally administered naturally oxidized olive oil once every 2 d for 2 weeks after ovalbumin (OVA)/aluminum hydroxide gel sensitization, after which ACA was elicited by intracutaneous administration of OVA into the ear auricles. Compared with fresh olive oil, oxidized olive oil administration increased the antigen-specific immunoglobulin E (IgE) antibody titer 2 weeks after OVA-sensitization and vascular hyperpermeability increased due to ACA. In the oxidized olive oil-administered mice, the mRNA expression levels of T-helper 2 (Th2) cytokines, interleukin (IL)-4, -5, -6, and -10, in the lymph nodes increased, as did the proportion of cluster designation (CD)3+CD4+ cells in the spleen and lymph nodes. In CD3+CD4+ cells, the mRNA expression levels of IL-4 and GATA-binding protein 3 (GATA3), the master regulator of Th2, were higher in the oxidized olive oil-group. Antigen-stimulated specific IL-4 production was promoted in CD3+CD4+ cells of oxidized olive oil-administered mice. This suggests that oxidized olive oil exacerbates ACA by promoting Th2 dominance in immediate allergic diseases.

PD-L1 Blockade During Allergen Sensitization Inhibits the Synthesis of Specific Antibodies and Decreases Mast Cell Activation in a Murine Model of Active Cutaneous Anaphylaxis.

Programmed cell death ligand 1(PDL-1) is known for its inhibitory effect on the cellular immune response. Even though it is expressed on the surface of mast cells, its role in allergic diseases is unknown. We analyzed the effects of PD-L1 blockade in a murine model of active cutaneous anaphylaxis (ACA). C57BL/6 mice were sensitized and challenged with ovalbumin (OVA). Blood samples were collected to measure specific immunoglobulins. The mice were divided into six groups that underwent the active cutaneous anaphylaxis procedure. Group 1 (negative control) received 50 µl of phosphate-buffered saline (PBS) subcutaneously, and the other five groups were sensitized with 50 µg of OVA subcutaneously. Group 2 was the positive control, and the others received the anti-PD-L1 antibody or its isotype during sensitization (groups 3 and 4) or during the challenge (groups 5 and 6). All animals that underwent ACA on the ears with OVA and PBS were sacrificed, and the reaction was evaluated by extravasation of Evans blue (measured by spectrophotometry) and histological analysis of the collected fragments. Anti-PD-L1 blockade during the sensitization phase led to a reduction in specific IgE and IgG1 levels, allergic reaction intensity at the ACA site, and mast cell degranulation in the tissue. There was no significant biological effect of anti-PD-L1 administration on the challenge phase. PD-L1 blockade during allergen sensitization inhibited the synthesis of specific IgE and IgG1 and decreased mast cell activation in this murine model of anaphylaxis.

Collagen-derived peptides modulate CD4+ T-cell differentiation and suppress allergic responses in mice.

INTRODUCTION: Collagen peptides have been widely used as a food supplement. After ingestion of collagen peptides, oligopeptides containing hydroxyproline (Hyp), which are known to have some physiological activities, are detected in peripheral blood. However, the effects of collagen-peptide administration on immune response are unclear. In the present study, we tested the effects of collagen-peptide ingestion on allergic response and the effects of collagen-derived oligopeptides on CD4+ T-cell differentiation. METHODS: BALB/c mice fed a collagen-peptide diet were immunized with ovalbumin (OVA), and their serum IgE and IgG levels, active cutaneous anaphylaxis, and cytokine secretion by splenocytes were examined. Naive CD4+ T cells were stimulated with anti-CD3 and anti-CD28 in the presence of collagen-derived oligopeptides, and the expression of IFN-γ, IL-4, and Foxp3 was analyzed. RESULTS: In an active anaphylaxis model, oral administration of collagen peptides suppressed serum OVA-specific immunoglobulin E (IgE) production and diminished anaphylaxis responses. In this model, the ingestion of collagen peptides skewed the pattern of cytokine production by splenocytes toward T-helper (Th) type 1 and regulatory T (Treg) cells. In vitro T-helper cell differentiation assays showed that Hyp-containing oligopeptides promoted Th1 differentiation by upregulating IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) signaling. These oligopeptides also promoted the development of Foxp3+ Treg cells in response to antigen stimulation in the presence of TGF-ß. CONCLUSIONS: Collagen-peptide ingestion suppresses allergic responses by skewing the balance of CD4+ T cells toward Th1 and Treg cells and seems to be a promising agent for preventing allergies and inflammatory diseases.