Figure 3.

Modulation of allergic sensitization and effector phase by n-3 LCPUFAs and fat-soluble vitamins, polyphenols and carotenoids. In in vitro and pre-clinical studies, the potency of n-3 LCPUFAs and several fat-soluble micronutrients to instruct DC silencing was indicated, rendering DCs that support Treg development. In addition, LPS or inflammatory induced maturation of DCs can be suppressed by multiple of these nutrients, resulting in reduced proliferation and activation of consequent effector T-cells responses, hence attenuating pro-inflammatory responses. Also, Th2 driven allergy development can be mitigated by these micronutrients, either by directly suppressing Th2 development or via enhancing Treg or Th1 responsiveness, known to down regulate Th2 activation. In addition, mast cell or basophil activation is modified or suppressed in various ways by n-3 LCPUFA and the selected fat-soluble micronutrients. Some micronutrients play an ambivalent role since they can lower pro-inflammatory responses via enhancing not only Treg but also Th2 function (VitD and VitA). This may be a point of concern in case of allergic predisposition. Of note is that the beneficial immunomodulatory effects of vitamin E are mainly linked to the alpha-tocopherol form and even though not much is known about immune effects of VitK, the main immunomodulatory effects appear to relate to the VitK2 isoform. These micronutrients can act via several receptors or signaling transduction cascades and are frequently tested as single component for their immunomodulatory capacities. However, since they target similar cells involved in the allergic sensitization and effector cascade their effects may by additive or synergistic when combined aiming to prevent allergy development or reduce severity of symptoms.