Biology subjects

Hahm, B.

Publications and source records attributed to Hahm, B..

3 recordsLinked to original sources

bioRxiv2026

Sphingosine 1-phosphate lyase expressed in pulmonary epithelial cells potentiates host innate defenses and alleviates influenza pathogenicity in mice

Influenza viruses circulate in humans, causing a substantial burden on global health. Investigation of influenza-host interactions could identify host factors that regulate influenza pathogenicity. Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator and regulates crucial cellular processes. S1P lyase (SPL), an enzyme that mediates S1P degradation, was shown to display anti-influenza activity in a cell culture system. Here, we constructed a mouse model to demonstrate the antiviral function of SPL in respiratory epithelial cells during influenza in vivo. Deletion of SPL from lung epithelial cells exacerbated influenza-induced weight loss and mortality. Influenza virus began to propagate more effectively in the absence of SPL at the innate immune stage. Increased virus titers were sustained during influenza and associated with enhanced accumulation of multiple immune cell types in the lungs. Single-cell RNA sequencing was conducted to further define the function of SPL in lung epithelial cells. SPL deletion increased the proportion of alveolar type 1 (AT1) cells compared to alveolar type 2 (AT2) cells with alteration of the related signaling pathways, suggesting a role of SPL in AT1/AT2 programming. Importantly, host innate defense pathways were changed in SPL-deficient lung epithelial cells upon infection, which corroborates the antiviral function of SPL. This study elucidates the host protective function of SPL in lung epithelial cells during influenza and provides gene signature profiles critical for SPL-mediated alleviation of influenza pathogenicity. The findings may contribute to development of host-directed therapeutics to better control influenza.

microbiology↗

bioRxiv2025

Sphingosine kinase 2 suppresses neutrophil responses to promote viral persistence while attenuating immune pathology

Chronic virus infections often suppress immune cell functions which helps in restricting immune pathology but leads to viral persistence. However, the underlying mechanisms are incompletely understood. We recently found that sphingosine kinase 2 (SphK2)-deficient (Sphk2-/-) mice succumbed to lymphocytic choriomeningitis virus (LCMV) infection due to immune pathology. In addition to heightened T cell immunity, a notable increase of neutrophils was observed in LCMV-infected Sphk2-/- mice. Depletion of neutrophils increased the viability of virus-infected Sphk2-/- mice, supporting a role of SphK2-deficient neutrophils in viral immune pathogenesis. Further, SphK2-deficient neutrophils expressed lower levels of the immune suppressive marker CD244 during infection. Importantly, adoptively transferred SphK2-deficient neutrophils demonstrated intrinsic regulation of CD244 and improved virus-specific T cell responses, resulting in diminished viral burden. Transcriptomic analysis revealed increased expression of pro-inflammatory and antiviral genes in SphK2-deficient neutrophils. These results indicate that SphK2 promotes suppressive neutrophil responses and regulates neutrophil-associated immune pathology during a persistent infection. Our findings may help design new immune therapeutics to control chronic viral diseases. SignificanceNeutrophils are the sentinels of the innate immune system; they can reshape innate and adaptive immune responses. During chronic illnesses, such as persistent viral infections, neutrophils can suppress the host immune response and help in disease progression. Here, we demonstrate regulation of neutrophil expansion and functions by sphingosine kinase 2 (SphK2) during LCMV infection. SphK2-deficient neutrophils express a reduced level of inhibitory receptor CD244, exert immune stimulatory effects on T cells, and promote virus clearance. Further, transcriptomic analysis reveals that SphK2 deficiency leads to the development of proinflammatory neutrophils. Our study identifies SphK2, a host factor, as being critical for neutrophil suppression that regulates dysfunctional T cell response and virus persistence.

immunology↗

bioRxiv2020

High frequency neuronal bursting is essential for circadian and sleep behaviors in Drosophila

Circadian rhythms have been extensively studied in Drosophila, however, still little is known about how the electrical properties of clock neurons are specified. We have performed a behavioral genetic screen through the downregulation of candidate ion channels in the lateral ventral neurons (LNvs) and show that the hyperpolarization-activated cation current Ih is important for the behaviors that the LNvs command: temporal organization of locomotor activity and sleep. Using whole-cell patch clamp electrophysiology we demonstrate that small LNvs are bursting neurons, and that Ih is necessary to achieve the high frequency bursting firing pattern characteristic of both types of LNvs. Since firing in bursts has been associated to neuropeptide release, we hypothesized that Ih would be important for LNvs communication. Indeed, herein we demonstrate that Ih is fundamental for the recruitment of PDF filled dense core vesicles to the terminals at the dorsal protocerebrum and for their timed release, and hence for the temporal coordination of circadian behaviors.

neuroscience↗