LAUSR

ABSTRACT Proteins and phenolic compounds can interact and form soluble and insoluble complexes. In this study, the complexation of whey protein isolate (WPI) with caffeic acid (CA) or (−)‐epigallocatechin‐3‐gallate (EGCG) is investigated as a strategy to attenuate oral sensitization in C3H/HeJ mice against WPI. Treatment with WPI‐CA reduced the levels of IgE, IgG1, IgG2a and mMCP‐1 in serum of mice measured by ELISA. This might be related to CD4+LAP+Foxp3+ T and IL‐17A+CD4+ T (Th17) cell activation, evidenced by flow cytometry of splenocytes. Treatment with WPI‐EGCG, in turn, decreased the levels of IgG2a and mMCP‐1 in serum of mice, possibly by the modulation of Th1/Th2 response and the increase of CD4+ Foxp3+ LAP− T and IL‐17A+CD4+ T (Th17) cell populations. In conclusion, WPI‐CA and WPI‐EGCG attenuated oral sensitization in C3H/HeJ mice through different mechanisms. We consider that the complexation of whey proteins with CA and EGCG could be a promising strategy to induce oral tolerance. HIGHLIGHTSWhey proteins (WPI)‐phenolic compound complexes attenuated oral sensitization to WPI.WPI‐caffeic acid and WPI‐EGCG reduced specific antibodies and mMCP‐1 in mice serum.Splenocytes from treated mice showed reduced in vitro proliferation of CD4+ T cells.Oral treatment with complexes activated regulatory T cells and IL‐17A+CD4+T cells (Th17).Complexation of WPI with CA or EGCG could be promising to induce oral tolerance.