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Histiocitosis de Erdheim Chester como desafío diagnóstico ante un cuadro sistémico: Reporte de un caso
(2024)
Dominga García
;
Yorman Flores
;
Maximiliano Vergara
;
Cristian Labarca Solar
Scopus© Citations 1
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Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-α2b in Healthy Adults: The IN2COVID Phase I Randomized Trial
(2023)
Diego Garcia-Huidobro
;
Carolina Iturriaga
;
Guillermo Perez-Mateluna
;
Paula Fajuri
;
Nicolás Severino
Scopus© Citations 2 1
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Protein kinase R is an innate immune sensor of proteotoxic stress via accumulation of cytoplasmic IL-24
(2022)
Sophia Davidson
;
Chien-Hsiung Yu
;
Annemarie Steiner
;
Frédéric Ebstein
;
Paul J. Baker
<jats:p>Proteasome dysfunction can lead to autoinflammatory disease associated with elevated type I interferon (IFN-αβ) and NF-κB signaling; however, the innate immune pathway driving this is currently unknown. Here, we identified protein kinase R (PKR) as an innate immune sensor for proteotoxic stress. PKR activation was observed in cellular models of decreased proteasome function and in multiple cell types from patients with proteasome-associated autoinflammatory disease (PRAAS). Furthermore, genetic deletion or small-molecule inhibition of PKR in vitro ameliorated inflammation driven by proteasome deficiency. In vivo, proteasome inhibitor–induced inflammatory gene transcription was blunted in PKR-deficient mice compared with littermate controls. PKR also acted as a rheostat for proteotoxic stress by triggering phosphorylation of eIF2α, which can prevent the translation of new proteins to restore homeostasis. Although traditionally known as a sensor of RNA, under conditions of proteasome dysfunction, PKR sensed the cytoplasmic accumulation of a known interactor, interleukin-24 (IL-24). When misfolded IL-24 egress into the cytosol was blocked by inhibition of the endoplasmic reticulum–associated degradation pathway, PKR activation and subsequent inflammatory signaling were blunted. Cytokines such as IL-24 are normally secreted from cells; therefore, cytoplasmic accumulation of IL-24 represents an internal danger-associated molecular pattern. Thus, we have identified a mechanism by which proteotoxic stress is detected, causing inflammation observed in the disease PRAAS.</jats:p>
Scopus© Citations 55 3
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Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells
(2021)
Vikas Duhan
;
Vishal Khairnar
;
Simo Kitanovski
;
Thamer A. Hamdan
;
KLEIN POSTERNACK, ANDRES DAVID
<jats:p>Early and strong production of IFN-I by dendritic cells is important to control vesicular stomatitis virus (VSV), however mechanisms which explain this cell-type specific innate immune activation remain to be defined. Here, using a genome wide association study (GWAS), we identified Integrin alpha-E (<jats:italic>Itgae</jats:italic>, CD103) as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 was specifically expressed by splenic conventional dendritic cells (cDCs) and limited IFN-I production in these cells during VSV infection. Mechanistically, CD103 suppressed AKT phosphorylation and mTOR activation in DCs. Deficiency in CD103 accelerated early IFN-I in cDCs and prevented death in VSV infected animals. In conclusion, CD103 participates in regulation of cDC specific IFN-I induction and thereby influences immune activation after VSV infection.</jats:p>
1Scopus© Citations 4

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