Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E

Abstract

These findings provide evidence that IL-33 induced secretion of IL-31 from LAD2 MC, an action augmented by novel neuroimmune interactions that may help in the development of new treatments of allergic and inflammatory diseases, especially AD and mastocytosis.

Regulation of the pleiotropic effects of tissue-resident mast cells

“…92 In the LAD2 human MC line, IL-4 pretreatment enhances IL-31 production after stimulation with IL-33. 91 These 2 studies are probably insufficient for generalization of IL-4-priming effects in IgE-independent signaling in human MCs but demonstrate that the priming effects are not restricted to FcεRI-mediated stimulation.…”

“…87 The priming effect of IL-4 is likely not restricted to intestinal or skin MCs but has been observed also in lung MCs, the human MC line LAD2, and other human MCs. [88][89][90][91] IL-4 is a key mediator of allergic inflammation, considering that it also induces development of T H 2 cells and IgE switching in B cells. 3 Thus SCF and IL-4 can be considered primary costimulatory mediators because they not only enhance FcεRI-mediated signals but also induce upregulation of secondary stimulatory receptors, such as the substance P (NK-1) receptor.…”

“…They might differ from triggers for human skin MCs or MCs from other species. 91,92 Important progress has been made in understanding MC regulation through the discovery of several inhibitory mechanisms that might balance the agonistic activities of mediators discussed previously. 194 Of particular relevance to the gastrointestinal tract are the anti-inflammatory cytokines TGF-b1 and IL-10, which are highly expressed in the healthy intestine.…”

Effect of IL-33 on de novo synthesized mediators from human mast cells

“…Recently, we reported that IL-33 augments allergen-induced secretion of IL-31, which is important in pruritus, as well as stimulates secretion of IL-31 from human mast cells in the absence of an allergic stimulus. 2 It is also pertinent to discuss the effect of IL-33 on nonallergic stimuli. We also showed that IL-33 augments the effect of the proinflammatory peptide substance P (SP) in stimulating secretion of impressive amounts of vascular endothelial growth factor (VEGF) 3 and TNF, 4 without concomitant secretion of tryptase, from human mast cells.…”

Atopic Dermatitis: Collegium Internationale Allergologicum (CIA) Update 2019

“…Histamine may induce pruritus by activating H1 and H4 receptors and inhibiting H3 receptor on skin-specific sensory nerves [14]. IL-31 that is produced by T cells and granulocytes such as eosinophils and mast cells, and which binds to its receptor on peripheral nerve fibers, has been shown to link inflammation and pruritus in the skin [15-17]. The observation that IL-31 induces an outgrowth of primary small-diameter dorsal root ganglia expressing abundant IL-31 receptor might explain the increased numbers of nerve fibers in AD skin and the sensitivity to minimal stimuli which induce itch in patients with AD [18, 19].…”