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

Abstract

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-β.

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.

Collagen-peptide feeding enhanced IFN-γ and IL-10 secretion by splenocytes. Mice fed a collagen peptide or control diet were immunized with OVA. Splenocytes from the immunized mice were cultured in the presence of OVA for 3 days and cytokine levels in the supernatant were measured.