Cytokine effects induced by the human autoallergen α-NAC

Autoallergy is a phenomenon found in a subgroup of patients with atopic dermatitis (AD). These patients exhibit serum IgE reactivity toward autoantigens like the alpha-chain of the nascent polypeptide-associated complex (α-NAC; Hom s 2). α-NAC has been shown before to induce T-cell proliferation and secretion of IFN-γ. To elucidate the immune modulating functions α-NAC may exert, we analyzed its effects on cytokine transcription and secretion in peripheral blood mononuclear cells (PBMCs), monocytes, and CD4+ T cells. Transcription and secretion of IFN-γ, IL-17, and IL-22 were increased in α-NAC-stimulated PBMCs. As IL-17 was significantly upregulated by α-NAC, we assessed signal transduction in PBMCs and found signal transducer and activator of transcription 3 phosphorylation in α-NAC-stimulated cells. Furthermore, we could show the importance of monocyte activation by α-NAC, as isolated T cells reacted only weakly toward the stimulation. Inhibition of IL-23 p19 led to lower amounts of IL-17 in the PBMC supernatants after α-NAC stimulation. α-NAC stimulation of PBMCs from non-allergic donors resulted in secretion of IL-10, which was greatly reduced in PBMCs from α-NAC-sensitized AD patients. Our findings provide insights into the mechanisms of autoallergy, investigating the interplay of immune cells, signaling events, and cytokines, which are known to be relevant in atopic skin inflammation.