IgG from atopic dermatitis patients induces non‐atopic infant thymic invariant natural killer T (iNKT) cells to produce IL‐4, IL‐17, and IL‐10

Abstract

Background Atopic dermatitis (AD) pathogenesis still needs to be elucidated, but invariant natural killer T (iNKT) cell involvement was already described by several groups. Our group has demonstrated that IgG antibodies purified from AD patients can modulate cytokine production by thymic T cells. Here we aimed to investigate if IgG from AD patients can modulate infant non-atopic thymic iNKT cells cytokine production in order to collaborate with the elucidation of AD development in infancy.Methods Thymic tissues were obtained from children from non-atopic mothers, and IgG was purified from AD patients diagnosed as moderate or severe and, as controls, from subjects clinically classified as non-atopic individuals. PBMCs from non-atopic individuals were also used in this study. ResultsOur results demonstrated that IgG from AD patients could induce non-atopic children thymic iNKT cells to produce higher levels of intracellular IL-4, IL-10, and IL-17 when compared to all control conditions. No effect was observed in non-atopic adults peripheral iNKT. We also observed that IgG from AD patients induces an increase in the expression of CD4 and Rorct transcription factor in non-atopic children thymic iNKT cells compared to the condition of all controls.Conclusions These observations suggest that IgG from AD patients can induce a cytokine profile by thymic iNKT cells from non-atopic infants compatible with the observations in AD development, which can collaborate with the elucidation of AD pathogenesis.

The Potential of IgG to Induce Murine and Human Thymic Maturation of IL-10+ B Cells (B10) Revealed in a Pilot Study

“…Extensive literature evidence demonstrates that the immune status of IgG donors may be related to differential modulation of thymic lymphocytes [ 26 , 31 , 45 , 46 ], which has been discussed in the literature since 2014 [ 6 , 47 ]. Among related observations, nonatopic IgG may be related to thymic maturation of lymphocytes with an allergy inhibition-related cytokine profile induced by γδT cells [ 48 ] as well as T CD4+ and CD8+ cells [ 5 ].…”

Do different IgG repertoires play a role in B‐ and T‐cell functional modulation during ontogeny? The “hooks without bait” theory

“…In the following years, it was also demonstrated that the IgG repertoire in patients who develop atopic dermatitis also modulates nonatopic human infant intrathymic abT and invariant natural killer T cells to produce a proinflammatory profile without influencing the proportions or viability of these cells. 89,90 This result suggests that IgG also influences the maturation of intrathymic abT and cells without causing cell depletion and making these cells more prone to inducing inflammatory disease.…”

Natural Self-Ligand Gamma Delta T Cell Receptors (γδTCRs) Insight: The Potential of Induced IgG

“…However, considering some breakthrough works in the literature demonstrating the differential effects of IgG repertoires on γδ T, αβ T, and B cells, we can observe a common characteristic that yields some additional speculation about this mechanism. The main described functional effects of IgG repertoires were obtained from chronic pathophysiological conditions including allergies [ 92 , 93 , 95 , 96 ], atopic dermatitis [ 94 , 97 ], or HIV-1-infected patients [ 111 ]. Considering those observations, we suggest that the γδTCR/IgG affinity determination results form a complex, long-term, and not yet clarified, process.…”

“…Another recent study has also demonstrated that IgG can modulate the production of IFN-γ and IL-10 by human thymic γδ T according to the donor’s immune status [ 93 ]. Corroborating this hypothesis, similar studies evaluating the potential of IgG molecules as mediators of modulatory effects on lymphocytes during their maturation have demonstrated several effects on human TCD4, TCD8, iNKT, and B cells [ 94 , 95 , 96 , 97 , 98 ].…”