Inhibitory impact of A1 and A2 cow’s milk on human peripheral blood mononuclear cells identifies TOM1 as a candidate anti-inflammatory mediator
Frontiers in Immunology, 2026
Flad L., Weißer T., Liedl J., Gard F., Petrera A., von Toerne C., Hauck S., Deeg C., Kleinwort K.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Nutritional Science | Pathophysiology | Cell Culture Supernatant |  Olink Target 48 |
Abstract
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 in vitro proliferation assays, we identified HWFs as the inhibitory fractions and analyzed the PBMC´s supernatant proteomes using high-resolution LC-MS/MS to assess changes in the cellular response to HWFs. Olink proteomics was used to asses the influence of the candidate protein on Immune-Response-Marker release of PBMC.
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 in vitro proliferation assays revealed an inhibitory impact of TOM1 on stimulated humane PBMC. Olink analysis of PBMC Immune-Response-Marker secretion reinforced a possible role for TOM1 as anti-inflammatory mediator in milk involved in the regulation of immune response via Interleukin-1β-associated signaling.
Discussion
Our findings provide new insights into milk-induced immune regulation and identify TOM1 as a promising anti-inflammatory factor.