Dataset Information

Mesenteric IL-10-producing CD5+ regulatory B cells suppress cow's milk casein-induced allergic responses in mice.

ABSTRACT: Food allergy is a hypersensitive immune reaction to food proteins. We have previously demonstrated the presence of IL-10-producing CD5(+) B cells and suggested their potential role in regulating cow's milk casein allergy in humans and IgE-mediated anaphylaxis in mice. In this study, we determined whether IL-10-producing CD5(+) regulatory B cells control casein-induced food allergic responses in mice and, if so, the underlying mechanisms. The induction of oral tolerance (OT) by casein suppressed casein-induced allergic responses including the decrease of body temperature, symptom score, diarrhea, recruitment of mast cells and eosinophils into jejunum, and other biological parameters in mice. Notably, the population of IL-10-producing CD5(+) B cells was increased in mesenteric lymph node (MLN), but not in spleen or peritoneal cavity (PeC) in OT mice. The adoptive transfer of CD5(+) B cells from MLN, but not those from spleen and PeC, suppressed the casein-induced allergic responses in an allergen-specific and IL-10-dependent manner. The inhibitory effect of IL-10-producing CD5(+) B cells on casein-induced allergic response was dependent on Foxp3(+) regulatory T cells. Taken together, mesenteric IL-10-producing regulatory B cells control food allergy via Foxp3(+) regulatory T cells and could potentially act as a therapeutic regulator for food allergy.

SUBMITTER: Kim AR

PROVIDER: S-EPMC4726293 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Mesenteric IL-10-producing CD5+ regulatory B cells suppress cow's milk casein-induced allergic responses in mice.

Kim A-Ram AR Kim Hyuk Soon HS Kim Do Kyun DK Nam Seung Taek ST Kim Hyun Woo HW Park Young Hwan YH Lee Dajeong D Lee Min Bum MB Lee Jun Ho JH Kim Bokyung B Beaven Michael A MA Kim Hyung Sik HS Kim Young Mi YM Choi Wahn Soo WS

Scientific reports 20160120

Food allergy is a hypersensitive immune reaction to food proteins. We have previously demonstrated the presence of IL-10-producing CD5(+) B cells and suggested their potential role in regulating cow's milk casein allergy in humans and IgE-mediated anaphylaxis in mice. In this study, we determined whether IL-10-producing CD5(+) regulatory B cells control casein-induced food allergic responses in mice and, if so, the underlying mechanisms. The induction of oral tolerance (OT) by casein suppressed ...[more]

PMID: 26785945

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Project description:BackgroundCow's milk protein allergy (CMPA) is one of the most common food allergies in infancy. Most infants with CMPA tolerate baked milk from diagnosis and gradually acquire increased tolerance. Nevertheless, parents often display significant anxiety about this condition and a corresponding reluctance to progress with home introduction of dairy due to concerns about possible allergic reactions.ObjectiveTo evaluate the impact on gradual home introduction of foods containing cows' milk after a supervised, single low-dose exposure to whole milk at time of diagnosis.MethodsInfants less than 12 months old referred with suspected IgE-mediated cow's milk allergy were recruited to an open-label randomized, controlled trial of intervention-a single dose of fresh cow's milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects-the ED05 - vs routine care. Both groups implemented graded exposure to CM (using the 12 step MAP Milk Tolerance Induction Ladder), at home. Parents completed food allergy quality of life questionnaires and State and Trait Anxiety Inventories (STAI). Main outcome measures were milk ladder position at 6 months and 12 months post-randomization.ResultsSixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months, 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p = .048). By 6 months, 11/37 (30%) intervention subjects had reached step 12 (i.e. drinking unheated cow's milk) compared to 2/20 (10%) of the controls (p = .049). Twelve months post-randomization, 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p = .03). Maternal STAIs were significantly associated with their infants' progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months.ConclusionThis study demonstrates the safety and effectiveness of introduction of baked milk implemented immediately after diagnosis of cows' milk allergy in a very young cohort. A supervised single dose of milk at the ED05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants' progress towards completion of the milk ladder, but pre-existing high levels of maternal anxiety are associated with poorer progress.

Project description:BackgroundA major protein component of cow's milk is β-casein. The most frequent variants in dairy herds are A1 and A2. Recent studies showed that milk containing A1 β-casein promoted intestinal inflammation and exacerbated gastrointestinal symptoms. However, the acute gastrointestinal effects of A1 β-casein have not been investigated. This study compared the gastrointestinal effects of milk containing A1 and A2 β-casein versus A2 β-casein alone in Chinese adults with self-reported lactose intolerance.MethodsIn this randomised, crossover, double-blind trial, with a 3-day dairy washout period at baseline, subjects were randomised to consume 300 mL of milk containing A1 and A2 β-casein (ratio 58:42; conventional milk) or A2 β-casein alone; subjects consumed the alternative product after a 7-day washout period. Urine galactose was measured at baseline after a 15 g lactose load. Subjects completed 9-point visual analogue scales for gastrointestinal symptoms (borborygmus, flatulence, bloating, abdominal pain, stool frequency, and stool consistency) at baseline and at 1, 3, and 12 h after milk consumption.ResultsA total of 600 subjects were included. All six symptom scores at 1 and 3 h were significantly lower after consuming A2 β-casein versus conventional milk (all P<0.0001). At 12 h, significant differences remained for bloating, abdominal pain, stool frequency, and stool consistency (all P<0.0001). Symptom scores were consistently lower with A2 β-casein in both lactose absorbers (urinary galactose ≥0.27 mmol/L) and lactose malabsorbers (urinary galactose <0.27 mmol/L).ConclusionMilk containing A2 β-casein attenuated acute gastrointestinal symptoms of milk intolerance, while conventional milk containing A1 β-casein reduced lactase activity and increased gastrointestinal symptoms compared with milk containing A2 β-casein. Thus, milk-related gastrointestinal symptoms may result from the ingestion of A1 β-casein rather than lactose in some individuals.Trial registrationNCT02878876 , registered August 16, 2016. Retrospectively registered.

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Dataset Information

Mesenteric IL-10-producing CD5+ regulatory B cells suppress cow's milk casein-induced allergic responses in mice.

Publications

Mesenteric IL-10-producing CD5+ regulatory B cells suppress cow's milk casein-induced allergic responses in mice.

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