Inhibitory impact of A1 and A2 cow's milk on human peripheral blood mononuclear cells identifies TOM1 as a candidate anti-inflammatory mediator.

Introduction: Cow´s milk has long been discussed as a modulator of immune response, with a particular focus on different health effects of its β-casein variants A1 and A2. To date, the factors in milk which may be responsible for effects on the human immune system remain unknown, revealing a lack of information that warrants further investigations. We previously found that both A1 and A2 milk inhibit Concanavalin A-induced human peripheral blood mononuclear cells (PBMC) proliferation. Accordingly, this study aimed to investigate the underlying mechanisms of the inhibitory effect. Methods: In a first step, we narrowed down the size-range of possible causative factors in A1 and A2 milk samples by separating each milk type in a high (> 100 kDa; HWF) and a low molecular weight fraction (< 100 kDa, LWF) and used them in co-incubation with Concanavalin A stimulated human PBMC. In Results: HWFs of milk exert an inhibitory effect on human PBMC. Among several candidates, Target of Myb protein 1 (TOM1) emerged as the only protein markedly increased in the supernatant proteomes after co-incubation with the HWFs of A1 and A2 milk. Further Discussion: Our findings provide new insights into milk-induced immune regulation and identify TOM1 as a promising anti-inflammatory factor.