Milk basic protein supplementation exerts an anti-inflammatory effect in a food-allergic enteropathy model mouse

• Published in: Journal of dairy science 2018-03, Vol.101 (3), p.1852-1863
• Main Authors: Ono-Ohmachi, Aiko, Nakajima-Adachi, Haruyo, Morita, Yoshikazu, Kato, Ken, Hachimura, Satoshi
• Format: Article
• Language: English
• Subjects: anti-inflammation; bone; food-allergic enteropathy; milk basic protein
• ISSN: 0022-0302; 1525-3198
• DOI: 10.3168/jds.2017-13253

To examine novel functions of milk basic protein (MBP) in T-cell-related inflammatory diseases, such as autoimmune diseases and allergies, we evaluated the effects of MBP on the causative responses of ovalbumin (OVA)-specific T cells in a food-allergic enteropathy model, OVA23–3 mice, which express an OVA-specific T-cell receptor gene. The OVA-specific CD4+ T cells of the mesenteric lymph nodes (MLN) from OVA23–3 mice were cultured with CD11c+ dendritic cells of MLN from BALB/cA mice in the absence or presence of MBP following stimulation with OVA; then the levels of CD69 expression and the levels of cytokine production by CD4+ T cells were measured to evaluate activation. The effects of MBP supplementation of OVA 23–3 mice were assessed by feeding a diet containing OVA (OVA diet) with or without MBP for 28 d. Intestinal inflammation, together with activation and cytokine production of CD4+ T cells by MLN, as well as femoral bone mineral density, were measured. In in vitro culture, MBP inhibited excess activation and IL-4 production by CD4+ T cells. The supplementation of MBP to the OVA diet attenuated OVA-specific IgE production in OVA-diet-fed OVA23–3 mice and slightly resolved developing enteropathy caused by excess IL-4 production by CD4+ T cells. Feeding OVA diet to OVA23–3 mice exhibited bone loss accompanied with enteropathy, whereas MBP supplementation prevented bone loss and increased osteoprotegerin, an osteoclastogenesis inhibitory factor, in the mice. The inhibition of T-cell-activation in both MLN and bone marrow by MBP supplementation may help prevent increased IgE levels caused by excessive IL-4 production and bone loss accompanied by enteropathy. Our findings show that MBP may help attenuate both T-cell-related inflammation and bone loss.