Biology subjects

Rodriguez-Morales, P.

Publications and source records attributed to Rodriguez-Morales, P..

3 recordsLinked to original sources

bioRxiv2026

Type I interferon primes the alveolar epithelium to receive reparative signals from tissue-resident macrophages

Lung repair in response to viral infection requires integrated communication between epithelial and immune compartments, yet the impact of antiviral mediators on epithelial regenerative capacity remains poorly defined. Here, we demonstrate that type I interferon (IFN-I) signaling primes the lung for alveolar renewal following viral challenge. IFN-I contributes to the induction of an interferon-stimulated gene-high (ISG)hi Sca-1Pos population of alveolar type II (ATII) epithelial cells. Sca-1Pos ATIIs exhibit enhanced proliferative capacity and increased organoid-forming efficiency compared with their Sca-1Neg counterparts. Viral challenge concurrently drives phenotypic reprogramming of tissueresident alveolar macrophages (trAMs). Sca-1Pos ATIIs display heightened responsiveness to oncostatin M (OSM) and, following viral challenge, require trAM-derived OSM for their proliferation. Together, these findings reveal that viral stimuli induce coordinated IFN-I-dependent epithelial and macrophage states that poise the lung for regeneration, positioning IFN-I not only as a central antiviral defense mechanism but as a priming signal that prepares lung tissue for renewal.

immunology↗

bioRxiv2023

Macrophages control pathological interferon responses during viral respiratory infection

Antiviral immune mediators, including interferons and their downstream effectors, are critical for host defense yet can become detrimental when uncontrolled. Here, we identify a macrophage-mediated anti-inflammatory mechanism that limits type I interferon (IFN-I) responses. Specifically, we found that cellular stress and pathogen recognition induce Oncostatin M (OSM) production by macrophages. OSM-deficient mice succumbed to challenge with influenza or a viral mimic due to heightened IFN-I activation. Macrophage-derived OSM restricted excessive IFN-I production by lung epithelial cells following viral stimulation. Furthermore, reconstitution of OSM in the respiratory tract was sufficient to protect mice lacking macrophage-derived OSM against morbidity, indicating the importance of local OSM production. This work reveals a host strategy to dampen inflammation in the lung through the negative regulation of IFN-I by macrophages. One-Sentence SummaryType I interferons induced by viral stimuli are negatively regulated by macrophage-derived Oncostatin M.

immunology↗

bioRxiv2020

Oxidized Lipids and CD36-Mediated Lipid Peroxidation in CD8 T Cells Suppress Anti-Tumor Immune Responses

T cell metabolic fitness plays a pivotal role in anti-tumor immunity and metabolic deregulation causes T cell dysfunction (i.e., exhaustion) in cancer. We identify that the scavenger receptor CD36 limits anti-tumor CD8+ T cell effector functions through lipid peroxidation. In murine tumors, oxidized phospholipids (OxPLs) were highly abundant and CD8+ TILs increased uptake and accumulation of lipids and lipid peroxidation. Functionally exhausted CD8+ TILs substantially increased CD36 expression and CD36-deficient CD8+ TILs had more robust anti-tumor activity and cytokine production than wild-type cells. We further show that CD36 promotes uptake of oxidized low-density lipoproteins (OxLDL) and induces lipid peroxidation in CD8+ TILs, and OxLDL inhibits CD8+ T cell functions in a CD36-dependent manner. Moreover, glutathione peroxidase 4 (GPX4) over-expression lowers lipid peroxidation and restores functionalities in CD8+ TILs. These results define a key role for an oxidized lipid-CD36 axis in promoting intratumoral CD8+ T cell dysfunction.

immunology↗