Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Eur J Immunol ; : e2350851, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38803021

RESUMO

Stress exposure has been shown to modulate innate and adaptive immune responses. Indeed, stress favors myelopoiesis and monocyte generation and contributes to cardiovascular disease development. As sex hormones regulate innate and adaptive immune responses, we decided to investigate whether stress exposure leads to a different immune response in female and male mice. Our data demonstrated that psychosocial stressinduced neutrophilia in male, but not female mice. Importantly, we identified that B-cell numbers were reduced in female, but not male mice upon exposure to stress. Thus, our study revealed that the stress-induced immune alterations are sex-dependent, and this is an important feature to consider for future investigations.

2.
Cell Stem Cell ; 30(6): 800-817.e9, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37267915

RESUMO

Cholesterol efflux pathways could be exploited in tumor biology to unravel cancer vulnerabilities. A mouse model of lung-tumor-bearing KRASG12D mutation with specific disruption of cholesterol efflux pathways in epithelial progenitor cells promoted tumor growth. Defective cholesterol efflux in epithelial progenitor cells governed their transcriptional landscape to support their expansion and create a pro-tolerogenic tumor microenvironment (TME). Overexpression of the apolipoprotein A-I, to raise HDL levels, protected these mice from tumor development and dire pathologic consequences. Mechanistically, HDL blunted a positive feedback loop between growth factor signaling pathways and cholesterol efflux pathways that cancer cells hijack to expand. Cholesterol removal therapy with cyclodextrin reduced tumor burden in progressing tumor by suppressing the proliferation and expansion of epithelial progenitor cells of tumor origin. Local and systemic perturbations of cholesterol efflux pathways were confirmed in human lung adenocarcinoma (LUAD). Our results position cholesterol removal therapy as a putative metabolic target in lung cancer progenitor cells.


Assuntos
Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Camundongos , Animais , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Colesterol/metabolismo , Neoplasias Pulmonares/genética , Proliferação de Células , Pulmão , Células-Tronco/metabolismo , Apolipoproteína A-I/metabolismo , Microambiente Tumoral
3.
Cell Rep ; 39(11): 110949, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35705045

RESUMO

Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.


Assuntos
Glândulas Suprarrenais , Macrófagos , Monócitos , Caracteres Sexuais , Glândulas Suprarrenais/metabolismo , Animais , Feminino , Antígenos de Histocompatibilidade Classe II/genética , Contagem de Leucócitos , Macrófagos/metabolismo , Masculino , Camundongos
4.
Nat Metab ; 3(10): 1313-1326, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34650273

RESUMO

Macrophages rely on tightly integrated metabolic rewiring to clear dying neighboring cells by efferocytosis during homeostasis and disease. Here we reveal that glutaminase-1-mediated glutaminolysis is critical to promote apoptotic cell clearance by macrophages during homeostasis in mice. In addition, impaired macrophage glutaminolysis exacerbates atherosclerosis, a condition during which, efficient apoptotic cell debris clearance is critical to limit disease progression. Glutaminase-1 expression strongly correlates with atherosclerotic plaque necrosis in patients with cardiovascular diseases. High-throughput transcriptional and metabolic profiling reveals that macrophage efferocytic capacity relies on a non-canonical transaminase pathway, independent from the traditional requirement of glutamate dehydrogenase to fuel ɑ-ketoglutarate-dependent immunometabolism. This pathway is necessary to meet the unique requirements of efferocytosis for cellular detoxification and high-energy cytoskeletal rearrangements. Thus, we uncover a role for non-canonical glutamine metabolism for efficient clearance of dying cells and maintenance of tissue homeostasis during health and disease in mouse and humans.


Assuntos
Aminação , Glutamina/metabolismo , Fosforilação Oxidativa , Animais , Camundongos , Fagocitose
5.
Nat Commun ; 12(1): 5255, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489438

RESUMO

Monocytes are part of the mononuclear phagocytic system. Monocytes play a central role during inflammatory conditions and a better understanding of their dynamics might open therapeutic opportunities. In the present study, we focused on the characterization and impact of monocytes on brown adipose tissue (BAT) functions during tissue remodeling. Single-cell RNA sequencing analysis of BAT immune cells uncovered a large diversity in monocyte and macrophage populations. Fate-mapping experiments demonstrated that the BAT macrophage pool requires constant replenishment from monocytes. Using a genetic model of BAT expansion, we found that brown fat monocyte numbers were selectively increased in this scenario. This observation was confirmed using a CCR2-binding radiotracer and positron emission tomography. Importantly, in line with their tissue recruitment, blood monocyte counts were decreased while bone marrow hematopoiesis was not affected. Monocyte depletion prevented brown adipose tissue expansion and altered its architecture. Podoplanin engagement is strictly required for BAT expansion. Together, these data redefine the diversity of immune cells in the BAT and emphasize the role of monocyte recruitment for tissue remodeling.


Assuntos
Tecido Adiposo Marrom/citologia , Monócitos/fisiologia , Adiponectina/genética , Tecido Adiposo Marrom/fisiologia , Animais , Diferenciação Celular/genética , Contagem de Leucócitos , Macrófagos/citologia , Macrófagos/fisiologia , Glicoproteínas de Membrana/metabolismo , Camundongos Transgênicos , Monócitos/citologia , Tomografia por Emissão de Pósitrons , Receptores CCR2/genética , Receptores CCR2/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA