JEFFERSON RUSSO VICTOR
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
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- Gamma-delta (gamma delta) T cell-derived cytokines (IL-4, IL-17, IFN-gamma and IL-10) and their possible implications for atopic dermatitis development(2023) FAGUNDES, Beatriz Oliveira; DE-SOUSA, Thamires Rodrigues; VICTOR, Jefferson RussoAtopic dermatitis (AD) is a chronic disease related to skin disorders that affect individuals in their childhood and can persist or start in adulthood. Patients affected by this disease commonly show skin lesions on the body surface (mainly on the upper and lower limbs) and allergic rhinitis or asthma crises. Looking at the disease from a molecular perspective, the major cytokines involved in inflammatory skin diseases, not only AD, include IL-4, IL-17, IFN-gamma and IL-10. Although they can produce these cytokines and infiltrate the affected epithelia in patients with AD, gamma delta T cells are still almost unexplored. In this update, we briefly discuss the involvement of IL-4, IL-17, IFN-gamma and IL-10 in the pathophysiology of AD and the possible role of gamma delta T cells during the inflammatory process.
- 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(2020) SANTOS, Ludimila S.; SGNOTTO, Fabio da Ressureicao; SOUSA, Thamires R.; ORFALI, Raquel L.; AOKI, Valeria; DUARTE, Alberto Jose da Silva; VICTOR, Jefferson R.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. Results Our 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 Ror gamma t 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.
- IgG from atopic dermatitis patients induces IL-17 and IL-10 production in infant intrathymic TCD4 and TCD8 cells(2018) SGNOTTO, Fabio D. R.; OLIVEIRA, Marilia G. de; LIRA, Aline A. L.; INOUE, Amanda H. S.; TITZ, Tiago O.; ORFALI, Raquel L.; BENTO-DE-SOUZA, Luciana; SATO, Maria N.; AOKI, Valeria; DUARTE, Alberto J. S.; VICTOR, Jefferson R.IntroductionOur group recently demonstrated that IgG modulates T cell cytokine production during the maturation process in the human thymus. The effects of this modulation are IgG repertoire dependent and can exert a systemic and long-term impact. ObjectiveTo investigate whether IgG from atopic dermatitis (AD) patients can modulate cytokine production of infant intrathymic TCD4 and TCD8 cells in vitro. MethodsThymic tissues were obtained from newborn children from nonatopic mothers, and thymocytes were cultured for 6 days with purified IgG from AD patients or with intravenous immunoglobulin (IVIG) or mock conditions as controls. Cells were gated as double positive T cells (TDP(-)CD4(+)CD8(+)), TCD4 cells (CD4(+)CD8(-)), or TCD8 cells (CD4(-)CD8(+)), and intracellular levels of IL-17A, IFN-, TNF-, IL-4, IL-10, and TGF- were evaluated by flow cytometry. ResultsCompared to mock and IVIG culture conditions, IgG of AD individuals induced in vitro intracellular production of IL-17 and IL-10 by intrathymic TDP, TCD4, and TCD8 cells of infants. TGF- was also detected at a higher frequency in response to AD IgG in TDP and TCD8 cells compared to mock and IVIG cultured conditions. An opposite effect was detected upon IFN- production in TCD4 cells, such that AD IgG reduced IFN- production compared to production under mock conditions but not under IVIG conditions. ConclusionIgG of AD patients can stimulate cytokine production in infant thymocytes and thus resembles the peripheral profile observed in adults. These findings suggest a novel mechanism that can contribute to AD pathogenesis.