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1.
Cell Mol Immunol ; 21(1): 80-90, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38082146

RESUMO

Regulatory T (Treg) cells play an essential role in maintaining immune balance across various physiological and pathological conditions. However, the mechanisms underlying Treg homeostasis remain incompletely understood. Here, we report that RIPK1 is crucial for Treg cell survival and homeostasis. We generated mice with Treg cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death. Unlike conventional T cells, Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis. However, simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways. Thus, our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis, thereby providing novel insights into the mechanisms of Treg cell homeostasis.


Assuntos
Apoptose , Linfócitos T Reguladores , Animais , Camundongos , Morte Celular , Homeostase
2.
Nat Commun ; 14(1): 8440, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114531

RESUMO

Autophagy receptor NDP52 triggers bacterial autophagy against infection. However, the ability of NDP52 to protect against viral infection has not been established. We show that NDP52 binds to envelope proteins of hepatitis B virus (HBV) and triggers a degradation process that promotes HBV clearance. Inactivating NDP52 in hepatocytes results in decreased targeting of viral envelopes in the lysosome and increased levels of viral replication. NDP52 inhibits HBV at both viral entry and late replication stages. In contrast to NDP52-mediated bacterial autophagy, lysosomal degradation of HBV envelopes is independent of galectin 8 and ATG5. NDP52 forms complex with Rab9 and viral envelope proteins and links HBV to Rab9-dependent lysosomal degradation pathway. These findings reveal that NDP52 acts as a sensor for HBV infection, which mediates a unique antiviral response to eliminate the virus. This work also suggests direct roles for autophagy receptors in other lysosomal degradation pathways than canonical autophagy.


Assuntos
Vírus da Hepatite B , Hepatite B , Humanos , Vírus da Hepatite B/fisiologia , Hepatócitos/metabolismo , Autofagia/fisiologia , Lisossomos/metabolismo , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/metabolismo , Replicação Viral/fisiologia
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