Research Grants 15/23395-6 - Imunogenética, Polimorfismo de um único nucleotídeo - BV FAPESP
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Immunogenetics of the inflammasome and translational study "from bed to bench and back": analysis of variations in inflammasome genes in monogenic and multifactorial autoinflammatory diseases for differential diagnosis and therapeutic applications

Abstract

The inflammasome plays a central role in the first defence the organism to pathogens and/or to injury/damage and mediates the inflammatory response by IL-1ß and IL-18 secretion. Conversely an excess of activation of the complex, and the consequent exacerbated production of these cytokines, is related both to the development of rare monogenic inflammatory diseases (auto-inflammatory syndromes) as well as of multifactorial diseases (autoimmune diseases, cancer, metabolic diseases, etc.), emphasizing that inflammatory mechanisms are an important trigger in the development of the most common diseases in the general population. Despite being well studied, most of the information nowadays available on the inflammasome derived from studies in experimental models, while little is known about the action of inflammasome in humans. Association studies about SNPs in inflammasome genes in patients with different multifactorial diseases revealed the contribution of one or another inflammasome in the pathogenesis of specific diseases, however there is a shortage of essential functional data to interpret these associations. In addition, the diagnosis of auto-inflammatory syndromes could benefit from a simpler and cheaper laboratory test than the sequencing of candidate genes, nowadays not disclosed by the Brazilian public health system. Considering these three aspects (association studies, lack of assays to study inflammasome in humans, and necessity of diagnostic tools for auto-inflammatory syndromes), in this project we intend to deepen the genetic contribution of inflammasome in the immune response modulation and in the pathogenesis and/or development of diseases with dysregulation of inflammation by association studies of multifactorial diseases, and by an in vitro assay for the study of inflammasome in primary human cells as a tool for the evaluation of the complex in different situations challenge or disease. This cellular assay will be imply to (a) evaluate the functional effects of genetic variants (b) confirm data obtained in animal models and (c) for clinical and translational research. (AU)

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Scientific publications (13)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
REIS, EDIONE C.; LEAL, VINICIUS N. C.; DA SILVA, LAIS T.; DOS REIS, MARILIA M. L.; ARGANARAZ, ENRIQUE R.; OSHIRO, TELMA M.; PONTILLO, ALESSANDRA. Antagonistic role of IL-1 beta and NLRP3/IL-18 genetics in chronic HIV-1 infection. Clinical Immunology, v. 209, . (15/23395-6, 13/06142-1, 15/50650-7)
GONCALVES CAMBUI, RAYLANE ADRIELLE; DO ESPIRITO SANTO, GILMAR FERREIRA; FERNANDES, FERNANDA PEREIRA; CORDEIRO LEAL, VINICIUS NUNES; GALERA, BIANCA BORSATTO; PALACIO FAVARO, EMERSON GIULIANO; RIZZO, LEONARDO AMORIM; ELIAS, ROSA MARIA; PONTILLO, ALESSANDRA. Double-edged sword of inflammasome genetics in colorectal cancer prognosis. Clinical Immunology, v. 213, . (15/50650-7, 15/23395-6)
DE LIMA, DHEMERSON SOUZA; NUNES, VINICIUS C. L.; OGUSKU, MAURICIO M.; SADAHIRO, AYA; PONTILLO, ALESSANDRA; ALENCAR, BRUNA DE CUNHA. Polymorphisms in SIGLEC1 contribute to susceptibility to pulmonary active tuberculosis possibly through the modulation of IL-1 beta. INFECTION GENETICS AND EVOLUTION, v. 55, p. 313-317, . (15/23395-6, 13/06142-1, 14/23225-0)
SOARES, JAINE L. S.; FERNANDES, FERNANDA PEREIRA; PATENTE, THIAGO ANDRADE; MONTEIRO, MARIA B.; PARISI, MARIA C.; GIANNELLA-NETO, DANIEL; CORREA-GIANNELLA, MARIA L.; PONTILLO, ALESSANDRA. Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?. Clinical Immunology, v. 187, p. 46-49, . (15/23395-6, 09/09276-3)
RODRIGUES, JULIANA DE MORAES; DE LIMA, DHEMERSON SOUZA; LEAL, VINICIUS N. C.; BOSCO, ADRIANA A.; SANDRIM, VALERIA; PONTILLO, ALESSANDRA. Gain-of-function SNPs in NLRP3 and IL1B genes confer protection against obesity and T2D: undiscovered role of inflammasome genetics in metabolic homeostasis?. ENDOCRINE, v. 60, n. 2, p. 368-371, . (15/23395-6)
DOS REIS, EDIONE CRISTINA; CORDEIRO LEAL, VINICIUS NUNES; DA SILVA SOARES, JAINE LIMA; FERNANDES, FERNANDA PEREIRA; DE LIMA, DHEMERSON SOUZA; DE ALENCAR, BRUNA CUNHA; PONTILLO, ALESSANDRA. Flagellin/NLRC4 Pathway Rescues NLRP3-Inflammasome Defect in Dendritic Cells From HIV-Infected Patients: Perspective for New Adjuvant in Immunocompromised Individuals. FRONTIERS IN IMMUNOLOGY, v. 10, . (15/23395-6, 18/04361-1, 15/17373-0, 14/23225-0, 17/10824-1)
SOARES, JAINE L. S.; OLIVEIRA, ENEDINA M. L.; PONTILLO, ALESSANDRA. Variants in NLRP3 and NLRC4 inflammasome associate with susceptibility and severity of multiple sclerosis. MULTIPLE SCLEROSIS AND RELATED DISORDERS, v. 29, p. 26-34, . (15/23395-6, 15/50650-7)
REIS, EDIONE C.; DA SILVA, LAIS T.; DA SILVA, WANESSA C.; RIOS, ALEXANDRE; DUARTE, ALBERTO J.; OSHIRO, TELMA M.; CROVELLA, SERGIO; PONTILLO, ALESSANDRA. Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 14, n. 8, p. 1995-2002, . (17/22131-0, 15/23395-6, 13/06142-1)
STEINER, ANNEMARIE; REYGAERTS, THOMAS; PONTILLO, ALESSANDRA; CECCHERINI, ISABELLA; MOECKING, JONAS; MOGHADDAS, FIONA; DAVIDSON, SOPHIA; CAROLI, FRANCESCO; GROSSI, ALICE; MORATO CASTRO, FABIO FERNANDES; et al. ecessive NLRC4-Autoinflammatory Disease Reveals an Ulcerative Colitis Locu. JOURNAL OF CLINICAL IMMUNOLOGY, v. 42, n. 2, . (15/50650-7, 15/23395-6)
MENDONCA, LEONARDO OLIVEIRA; MARAGNA TOLEDO-BARROS, MYRTHES ANNA; CORDEIRO LEAL, VINICIUS NUNES; GISLENE VERA ROA, MARIELA ESTEFANY; GONCALVES CAMBUI, RAYLANE ADRIELLE; TOLEDO, ELIANA; BARROS, SAMAR FRESCHI; DE OLIVEIRA, AMANDA MELATO; RIVITTI-MACHADO, MARIA CECILIA; MEDEIROS FRANCESCANTONIO, ISADORA CARVALHO; et al. In-vitro NLRP3 functional test assists the diagnosis of cryopyrin-associated periodic syndrome (CAPS) patients: A Brazilian cooperation. Clinical Immunology, v. 245, p. 8-pg., . (15/23395-6, 19/06363-4)
CORDEIRO LEAL, VINICIUS NUNES; REIS, EDIONE CRISTINA; FERNANDES, FERNANDA PEREIRA; DA SILVA SOARES, JAINE LIMA; COSTA OLIVEIRA, IOHANA GABRIELY; DE LIMA, DHEMERSON SOUZA; LARA, AMANDA NAZARETH; LOPES, MARTA HELOISA; PONTILLO, ALESSANDRA. Common pathogen-associated molecular patterns induce the hyper-activation of NLRP3 inflammasome in circulating B lymphocytes of HIV-infected individuals. AIDS, v. 35, n. 6, p. 899-910, . (15/23395-6, 18/04361-1, 15/50650-7, 15/17373-0, 17/10824-1)
REIS, ARAMYS S.; BARBOZA, RENATO; MURILLO, OSCAR; BARATEIRO, ANDRE; PEIXOTO, ERIKA P. M.; LIMA, FLAVIA A.; GOMES, VINICIUS M.; DOMBROWSKI, JAMILLE G.; LEAL, VINICIUS N. C.; ARAUJO, FRANCIELE; et al. Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes. SCIENCE ADVANCES, v. 6, n. 10, . (14/09964-5, 15/23395-6, 14/20451-0, 17/03939-7, 11/19048-8, 17/05782-8, 13/16417-8, 16/07030-0, 12/16525-2, 12/04755-3, 15/50650-7, 18/20468-0, 13/00981-1, 11/17880-8, 15/06106-0)
DE LIMA, DHEMERSON SOUZA; BOMFIM, CAIO C. B.; LEAL, VINICIUS N. C.; REIS, EDIONE C.; SOARES, JAINE L. S.; FERNANDES, FERNANDA P.; AMARAL, EDUARDO P.; LOURES, V, FLAVIO; OGUSKU, MAURICIO M.; D'IMPERIO LIMA, MARIA R.; et al. Combining Host Genetics and Functional Analysis to Depict Inflammasome Contribution in Tuberculosis Susceptibility and Outcome in Endemic Areas. FRONTIERS IN IMMUNOLOGY, v. 11, . (15/20432-8, 15/23395-6, 15/50650-7)

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