Cristiane Naffah de Souza | University of Sao Paulo (original) (raw)
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Papers by Cristiane Naffah de Souza
Immune cell infiltration in (white) adipose tissue (AT) during obesity is associated with the dev... more Immune cell infiltration in (white) adipose tissue (AT) during obesity is associated with the development of insulin resistance. In AT, the main population of leukocytes are macrophages. Macrophages can be classified into two major populations: M1, classically activated macrophages, and M2, alternatively activated macrophages, although recent studies have identified a broad range of macrophage subsets. During obesity, AT M1 macrophage numbers increase and correlate with AT inflammation and insulin resistance. Upon activation, pro-inflammatory M1 macrophages induce aerobic glycolysis. By contrast, in lean humans and mice, the number of M2 macrophages predominates. M2 macrophages secrete anti-inflammatory cytokines and utilize oxidative metabolism to maintain AT homeostasis. Here, we review the immunologic and metabolic functions of AT macrophages and their different facets in obesity and the metabolic syndrome.
Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by... more Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to α-galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-γ and interleukin (IL)-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jα18KO and IFN- γKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jα18KO mice exhibited renal dys- function, but adenine-fed Jα18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration.
A hipertensão arterial sistêmica (HAS) é fator agravante para a ocorrência de acidente vascular e... more A hipertensão arterial sistêmica (HAS) é fator agravante para a ocorrência de acidente vascular encefálico (AVE) e pode provocar no coração hipertro a e brose e no rim, nefroescle- rose. Foram registrados 41 casos de pacientes hipertensos no período de 1985 a 2004. Selecionaram-se 23 casos que apresentavam os fragmentos de coração e rim para a análise morfológica. As lâminas foram coradas com picrossírius e quanti cadas as porcentagens de brose cardíaca (%FC) e renal (%FR). A pressão arterial média (PAm) foi calculada segundo a fórmula: PAm (pressão arterial média) = PD (pressão diastólica) + (OS (pressão sistólica)-PD)/3. Foram encontrados 17 (73,9%) casos de AVE, dos quais 8 foram hemorrágicos (47%), 2, isquêmicos (11,7%) e 7 (41,2%) não tinham descrição do tipo. A média da PAm foi de 135,3 mmHg nos pacientes com AVE (147,1 no hemorrágico e 88,3 no isquêmico; p = 0,036) e de 97,9 mmHg nos sem AVE (p = 0,032). A mediana da %FR nos pacientes com AVE foi de14,3enossemAVEfoide13,9(p=0,878),ada%FCfoi de 1,7 e 0,3 (p = 0,205), respectivamente. As correlações entre %FC e %FR com PAm foram positivas (rS = 0,253 e p = 0,305; r = 0,167 e p = 0,508, respectivamente). Os pacientes com AVE, especialmente o hemorrágico, e os que tiveram maior %FC e %FR apresentaram níveis mais elevados de PAm, PA sistólica e glicemia. Portanto, esses fatores estariam relacionados ao acometimento mais intenso dos órgãos-alvo da HAS. Porém, as análises da %FC e %FR mostram que a ocorrência de AVE não está relacionada à intensidade da lesão nos outros órgãos-alvo.
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They... more Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, co- mmensal microbiota tolerance, tissue repair and in- flammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.
Immune cell infiltration in (white) adipose tissue (AT) during obesity is associated with the dev... more Immune cell infiltration in (white) adipose tissue (AT) during obesity is associated with the development of insulin resistance. In AT, the main population of leukocytes are macrophages. Macrophages can be classified into two major populations: M1, classically activated macrophages, and M2, alternatively activated macrophages, although recent studies have identified a broad range of macrophage subsets. During obesity, AT M1 macrophage numbers increase and correlate with AT inflammation and insulin resistance. Upon activation, pro-inflammatory M1 macrophages induce aerobic glycolysis. By contrast, in lean humans and mice, the number of M2 macrophages predominates. M2 macrophages secrete anti-inflammatory cytokines and utilize oxidative metabolism to maintain AT homeostasis. Here, we review the immunologic and metabolic functions of AT macrophages and their different facets in obesity and the metabolic syndrome.
Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by... more Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to α-galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-γ and interleukin (IL)-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jα18KO and IFN- γKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jα18KO mice exhibited renal dys- function, but adenine-fed Jα18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration.
A hipertensão arterial sistêmica (HAS) é fator agravante para a ocorrência de acidente vascular e... more A hipertensão arterial sistêmica (HAS) é fator agravante para a ocorrência de acidente vascular encefálico (AVE) e pode provocar no coração hipertro a e brose e no rim, nefroescle- rose. Foram registrados 41 casos de pacientes hipertensos no período de 1985 a 2004. Selecionaram-se 23 casos que apresentavam os fragmentos de coração e rim para a análise morfológica. As lâminas foram coradas com picrossírius e quanti cadas as porcentagens de brose cardíaca (%FC) e renal (%FR). A pressão arterial média (PAm) foi calculada segundo a fórmula: PAm (pressão arterial média) = PD (pressão diastólica) + (OS (pressão sistólica)-PD)/3. Foram encontrados 17 (73,9%) casos de AVE, dos quais 8 foram hemorrágicos (47%), 2, isquêmicos (11,7%) e 7 (41,2%) não tinham descrição do tipo. A média da PAm foi de 135,3 mmHg nos pacientes com AVE (147,1 no hemorrágico e 88,3 no isquêmico; p = 0,036) e de 97,9 mmHg nos sem AVE (p = 0,032). A mediana da %FR nos pacientes com AVE foi de14,3enossemAVEfoide13,9(p=0,878),ada%FCfoi de 1,7 e 0,3 (p = 0,205), respectivamente. As correlações entre %FC e %FR com PAm foram positivas (rS = 0,253 e p = 0,305; r = 0,167 e p = 0,508, respectivamente). Os pacientes com AVE, especialmente o hemorrágico, e os que tiveram maior %FC e %FR apresentaram níveis mais elevados de PAm, PA sistólica e glicemia. Portanto, esses fatores estariam relacionados ao acometimento mais intenso dos órgãos-alvo da HAS. Porém, as análises da %FC e %FR mostram que a ocorrência de AVE não está relacionada à intensidade da lesão nos outros órgãos-alvo.
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They... more Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, co- mmensal microbiota tolerance, tissue repair and in- flammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.