Cytokines and Soluble Receptors in Breast Milk as Enhancers of Oral Tolerance Development

Abstract

The postpartum period is an important window during which environmental factors can shape the life-long health of the infant. This time period often coincides with substantial milk consumption either in the form of breast milk or from cow's milk sources, such as infant formulas. Although breast milk is the most beneficial source of nutrients for infants during the first 6 months after birth, its role in regulating food allergy development, through regulation of oral tolerance, is still controversial. Breast milk contains several factors that can impact mucosal immune function, including immune cells, antibodies, microbiota, oligosaccharides, cytokines, and soluble receptors. However, there is considerable variation in the assessed levels of cytokines and soluble receptors between studies and across the lactation period. Most of these cytokines and soluble receptors are absent, or only found in limited quantities, in commercial baby formulas. Differences in content of these pluripotent factors, which impact on both the mother and the neonate, could contribute to the controversy surrounding the role of breast milk regulating oral tolerance. This review highlights current knowledge about the importance of cytokines and soluble receptors in breast milk on the development of oral tolerance and tolerance-relateddisorders. Understanding the mechanisms by which such milk components might promote oral tolerance could aid in the development of improved strategies for allergy prevention.

A role for early oral exposure to house dust mite allergens through breast milk in IgE-mediated food allergy susceptibility

“…However, we cannot formally conclude that D pteronyssinus proteases are solely responsible for the cascade of immune events that are occurring in offspring nursed by D pteronyssinus-exposed mothers and other immune modulatory molecules in breast milk of D pteronyssinus-exposed mothers may play an additional role. 55,56 The observation that milk of mothers exposed to D pteronyssinus displayed an increased proteolytic activity using Der p 1 preferential substrate as compared to milk of PBS-exposed mothers or to milk of mothers exposed to D pteronyssinus allergen with no protease activity (protease-inactivated D pteronyssinus) suggests that maternal exposure to D pteronyssinus protease results in its transfer to the milk. We further confirmed that the increased proteolytic activity found in D pteronyssinuscontaining breast milk was not related to the potential release of mast-cell tryptase by neonates exposed to D pteronyssinus as similar levels of tryptase were found in milk collected from the stomach of pups nursed by mothers exposed to PBS or D pteronyssinus (data not shown).…”

Bioactive Factors in Human Breast Milk Attenuate Intestinal Inflammation during Early Life

“…TGF-β inhibits naïve T cells from differentiation into Th1 and Th2 subtypes, which promote cell mediated immune responses by secreting pro-inflammatory cytokines and promote IgE and eosinophilic responses, respectively. TGF-β also helps stabilize forkhead box P3 (FOXP3) expression and maintains the differentiation of T-regulatory cells which inhibit immune responses and temper inflammation [63]. In preterm infants, lower TGF-β levels preceded NEC development, underlining the significance of TGF-β in immune and inflammation regulation [64].…”

More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects

“…However, the key anti-inflammatory and immunoregulatory cytokine interleukin-10 (IL-10), is found in very high concentrations during the first 80 hours of lactation (Garofalo et al 1995). It has been suggested that IL-10 inhibits Th1 responses, contributes to the survival and expansion of B cells, and downregulates major histocompatibility complex-II (MHC-II) expression on monocytes (Dawod and Marshall 2019). Another regulatory cytokine found in breast milk is IL-7.…”