Mitochondrial phosphatase PGAM5 negatively regulates IL-4-induced anti-inflammatory responses and metabolic reprogramming of macrophages by controlling JAK

CD22 regulates IL-4–induced expansion and responsiveness of virtual memory T cells during helminth infection.

This study reports that exosomes produced by IL4-polarized THP-1 human macrophages (THP1-IL4-exo) can serve to reverse cardiac functional decline in mice with heart failure caused by diet-induced myocardial infarction (MI). Ng and colleagues identify Type 1 Interferon signaling as a key pathway attenuated by THP1-IL4-exo, responsible for conferring cardioprotection post-MI.

Respiratory syncytial virus (RSV) poses a considerable health burden to pediatric and elderly populations, but vaccine development is hindered by the risk of enhanced respiratory disease (ERD) and limitations of current animal models.MethodsSyrian hamsters of different ages were intranasally inoculated with RSV to establish an age-stratified model. Additionally, old hamsters were immunized with heat-inactivated RSV (HI-RSV) for ERD research. Disease pathogenesis was assessed through symptom monitoring, viral load quantification, histopathological examination, and transcriptomic analysis.ResultsRSV infection induced coughing-like symptoms in adult and old hamsters. Neonates exhibited significant growth retardation, the most pronounced viral replication and delayed viral clearance, and prolonged bronchiolitis-like lung injury. HI-RSV vaccination in old hamsters resulted in classic ERD, characterized by enhanced lung pathology, eosinophil infiltration, and mucus overproduction. Further transcriptomic profiling revealed upregulation of pathways related to Th1/Th2 cell differentiation, with marked increases in Th2 cytokines (Il4, Il5, and Il13) and associated transcription factors (Jak3, GATA binding protein 3, and Runt-related transcription factor 3), mechanistically linking Th2-biased immunity to ERD.ConclusionsOur findings confirm the relevance of using Syrian hamsters to study age-dependent RSV pathogenesis and to evaluate the safety of RSV vaccines, particularly with regard to the risk of ERD associated with Th2-biased immune responses.

Fang et al. showed that GM-CSF–IL4, commonly used to differentiate bone marrow cells into DCs in vitro for use in vaccines, induced differentiation of DCs to express ALDH1A2 and produce retinoic acid...

Respiratory syncytial virus (RSV) poses a considerable health burden to pediatric and elderly populations. Vaccine development has been historically challenged by the risk of enhanced respiratory disease (ERD), and existing animal models often fail to adequately recapitulate human disease.MethodsSyrian hamster were established as a translational model for studying age-stratified RSV infection and vaccine-associated ERD. Animals of different ages were intranasally inoculated with RSV. Additionally, old hamsters were immunized with heat-inactivated RSV (HI-RSV) for ERD research. Disease pathogenesis was assessed through symptom monitoring, viral load quantification, histopathological examination, and transcriptomic analysis.ResultsRSV infection induced coughing-like symptoms in adult and old hamsters. Neonates exhibited significant growth retardation, the most pronounced viral replication and delayed viral clearance, and prolonged bronchiolitis-like lung injury. HI-RSV vaccination in old hamsters resulted in classic ERD, characterized by enhanced lung pathology, eosinophil infiltration, and mucus overproduction. Further transcriptomic profiling revealed upregulation of pathways related to Th1/Th2 cell differentiation, with marked increases in Th2 cytokines (Il4, Il5, Il13) and associated transcription factors (Jak3, Gata3, Runx3), mechanistically linking Th2-biased immunity to ERD.ConclusionsOur findings confirm the relevance of using Syrian hamsters to study age-dependent RSV pathogenesis and to evaluate the safety of RSV vaccines, particularly with regard to the risk of ERD associated with Th2-biased immune responses.