Profa. Dra. Sonia Jancar Negro

Título: Professora Titular
Laboratório: Imunofarmacologia
Telefone: 55 (11) 3091-7744
E-mail: sojancar@icb.usp.br
Lattes: https://sistemas.usp.br/tycho/CurriculoLattesMostrar?codpub=B7A0AE35DF1B

Alunos

Ildefonso Alves da Silva Jr – Pós-doutorando FAPESP
Theresa Raquel de Oliveira Ramalho – Doutoranda CNPq
João Pedro Tôrres Guimarães – Doutorando CAPES
Ana Carolina Chiacetti Rodrigues – Mestranda FAPESP
Nayara Pereira – Mestranda CNPq
Marlise Montes – Especialista de Laboratório

Resumo da linha de pesquisa

Macrófagos e células dendríticas (DCs) apresentam receptores de membrana(PRRs) que reconhecem estruturas microbianas, a família de receptores toll-like sendo os receptores prototípicos deste grupo. Outro grupo de PRRs reconhece moléculas e células próprias alteradas tais como lipídeos oxidados e células mortas e, deste grupo, o CD36 é o receptor mais estudado. A estimulação destes receptores induz a síntese imediata de mediadores lipídicos (prostaglandinas, leucotrienos e PAF) seguido de transcrição de vários genes. Macrófagos e DCs desempenham um papel central no desenvolvimento, homeostasia, reparo tecidual e resposta imune. Estas células possuem alta plasticidade mudando seu estado funcional de acordo com estímulos do microambiente. Evidências de trabalhos do nosso grupo e de outros sugerem que a estimulação autócrina de receptors para mediadores lipídicos, em associação com a ativação de PRRs, é capaz de modular o fenótipo de macrófagos e DCs. No presente estudo nos propomos a investigar o efeito da associação: a) PAFR/CD36 nas células do microambiente tumoral; b) PAFR/CD36 na imunossupressão associada a tumores; c) PAFR/CD36 na resposta de tumores a quimioterapia e irradiação; d) PAFR/TLR4 em células dendríticas e na resposta imune in vivo; e) PAFR/TLRs no fenótipo de macrófagos; f) receptor para LTB4/TLR4 em macrófagos e seu efeito na inflamação e resistência a insulina em diabéticos tipo 1. Avanços no conhecimento das interações entre PRRs e receptores para mediadores lipídicos permitiriam a modulação farmacológica de modo a ajustar o fenótipo dos macrófagos e DCs para controlar a obesidade e doenças relacionadas, resolver fibroses, tratar o câncer e modular a resposta imune adaptativa.

Research descriptions

Macrophages and dendritic cells (DCs) present membrane receptors (PRRs) that recognize microbial structures, Toll-like receptor family being the prototypic receptors of this group. Another group of PRRs recognize altered self components such as oxidized lipids and dying cells and among them the CD36 was the most studied. Stimulation of these receptors induces early generation of lipid mediators (prostanoids, leukotrienes and PAF), cytokine genes transcription. Macrophages and DCs have a central role in development, homeostasis, tissue repair and immune response. They possess high plasticity changing their functional state according to microenvironment stimuli. Evidence from our group and others suggests that autocrine stimulation of receptors for lipid mediators in association with PRRs, is able to modulate macrophages and DCs phenotype. In the present study we will investigate the effect of: a) PAFR/CD36 association in tumor microenvironment cells; b) PAFR in tumor-associated immunosuppression and tumor response to chemotherapy and irradiation; c) PAFR/TLR4 association in DCs function and immune responses in vivo; PAFR association with TLRs on macrophages phenotype and functions; c) macrophages LTB4/TLR4 association in inflammation and insulin resistance in type 1 diabetes. Advances in the knowledge of the mechanisms involved in the phenotypic changes would allow therapeutic targeting of macrophages and DCs to adjust their phenotype to control obesity and related diseases, resolve fibrosis, treat cancer and modulate the adaptive immune response.

Principais publicações

da Silva-Junior IA(1), Dalmaso B(1), Herbster S(1), Lepique AP(1), Jancar S. Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation-Induced Cell Death. FRONT ONCOL. v. 5, p 8:10. 2018.
Chammas, R; Andrade, L; Jancar, S. Oncogenic effects of PAFR ligands produced in tumours upon chemotherapy and radiotherapy. NATURE REVIEWS CANCER,v.17 (4) p. 253, 2017
Da Silva-Jr, I A; Chammas, R; Lepique, A P; Jancar, S. Platelet-activating factor (PAF) receptor as a promising target for cancer cell repopulation after radiotherapy. NATURE ONCOGENESIS, v. 6, p. e296, 2017.
da Silva Junior IA^,Stone SC, Rossetti RM^,Jancar S,^,Lepique AP. Modulation of Tumor-Associated Macrophages Phenotype by Platelet-Activating Factor (PAF) Receptor. IMMUNOL. RES. v. 2017:p.5482768, 2017
Koga, M. M; Bizzarro, B.; Sá-Nunes, A.; Rios, F. J. ; Jancar, S. Boosting Adaptive Immunity: A New Role for PAFR Antagonists. SCIENTIFIC REPORTS, v. 6, p. 39146, 2016.
Filgueiras, L. R; Brandt, S. L.; De Oliveira R, T. R ; Jancar, S; Serezani, C. H. Imbalance between HDAC and HAT activities drives aberrant STAT1/MyD88 expression in macrophages from type 1 diabetic mice. JOURNAL OF DIABETES AND ITS COMPLICATIONS, v. 31(2), p. 3334, 2017.
Ishizuka EK, Filgueiras LR, Rios FJ, Serezani CH, Jancar S. .PAFR activation of NF-κB p65 or p105 precursor dictates pro- and anti-inflammatory responses during TLR activation in murine macrophages. SCIENTIFIC REPORTS 24;6:32092, 2016
Filgueiras, L. R. ; Brandt, S. L. ; Wang, S. ;Evans-Molina, C. ; Mirmira, R. G. ; Jancar, S. ; Serezani, C. H. . Leukotriene B4-mediated sterile inflammation promotes susceptibility to sepsis in a mouse model of type 1 diabetes. SCIENCE SIGNALING, v. 8, p. ra10, 2015.
Filgueiras, L. R; Serezani, C. H; Jancar, S. Leukotriene B4 as a Potential Therapeutic Target for the Treatment of Metabolic Disorders. FRONTIERS IN IMMUNOLOGY (Online), v. 6, p. 515, 2015.
Filgueiras LR, Capelozzi VL, Martins JO, Jancar S. Sepsis-induced lung inflammation is modulated by insulin. BMC PULM.; v.14: p. 177, 2014