Biology subjects

Nishibori, M.

Publications and source records attributed to Nishibori, M..

3 recordsLinked to original sources

bioRxiv2026

Hmgb1 release kinetics shape its extracellular functions during regulated cell death

Danger-associated molecular patterns (DAMPs), such as high mobility group protein B1 (HMGB1), are released from dying cells, yet the kinetics and functional consequences of their release remain unclear. Using Hmgb1-mCherry transgenic mice and live-cell imaging, we visualize Hmgb1 and interleukin-1{beta} (IL-1{beta}) secretion at single-cell resolution. Hmgb1 exhibits two distinct release kinetics: short-duration completed within 1 min and long duration spanning several minutes. Mathematical modeling demonstrates that short-duration release generates substantially higher local Hmgb1 concentrations and steeper gradients near the dying cell than long-duration release. Such rapid release may enable one or a few dying cells to produce sufficient Hmgb1 to stimulate neighboring cells, consistent with its role as an alarmin. In vivo imaging of cisplatin-induced kidney injury reveals an inverse correlation between intracellular Hmgb1 levels and monocyte infiltration. Together, these findings suggest that Hmgb1 release kinetics shape its extracellular functions during regulated cell death.

cell biology↗

bioRxiv2021

Insights on the historical biogeography of Philippine native pigs and its relationship with Continental domestic and wild boars

The Philippine archipelago was believed to have never been connected to the Asian continent even during the severe Quaternary sea-level drops. As a result, the history of pig dispersal in the Philippines remains controversial and must have some anthropogenic origin associated with some human migration events. In this study, the context of origin, dispersal, and the level of genetic introgression in Philippine native pigs were deduced using mitochondrial DNA D-loop analysis altogether with domestic pigs and wild boars corresponding to their geographic origin. Results revealed a considerable genetic diversity (0.900{+/-}0.016), and a widespread Asian pig-ancestry (94.60%) were revealed in the phylogenetic analysis with admixed European pig-origin (5.10%) harboring various fractions of ancestry from Berkshire and Landrace. The close genetic connection between the continental wild boars and domestic pigs present in the Philippine pigs corroborates our hypothesis of a genetic signal that could potentially be associated with the recently reported multiple waves of human migrations to the Philippines during the last 50,000 years. The high frequency of haplotypes (54.08%) that collapsed in the D7 haplogroup represent an interesting challenge as its distribution does not coincide with the hypothesized migratory route of the Neolithic Austronesian-speaking populations. We detected the first Pacific Clade signature and ubiquitously distributed D2 haplotypes which postulate the legitimate dispersal of pigs associated with the multiple waves of human migrations involving the Philippines. The multimodal mismatch and neutrality test statistics both Fus Fs and Tajimas D correlates the long stationary period of effective population size revealed in the Bayesian skyline plot. While the sudden decrease in population was consistent with the pronounced population bottleneck of Asian and European pigs during the interglacial periods of the Pleistocene.

zoology↗

bioRxiv2019

Leukocyte-derived High-mobility group box 1 controls innate immune responses against Listeria monocytogenes.

High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern with key proinflammatory functions following tissue injury. Moreover, HMGB1 neutralization was shown to alleviate LPS-induced shock, suggesting a role for the protein as a master therapeutic target for inflammatory and infectious diseases. Here, we report that HMGB1 neutralization impedes immune responses to Listeria monocytogenes, a wide-spread bacterium with pathogenic relevance for humans and rodents. Using genetic deletion strategies and neutralizing antibodies, we demonstrate that hepatocyte HMGB1, a major driver of post-necrotic inflammation in the liver, is dispensable for pathogen defense during moderately severe infection with listeria. In contrast, antibody-mediated HMGB1 neutralization and HMGB1 deficiency in myeloid cells effectuate rapid and uncontrolled bacterial dissemination in mice despite preserved basic leukocyte functionality and autophagy induction. During overwhelming infection, hepatocyte injury may contribute to increased HMGB1 serum levels and excessive inflammation in the liver, supporting context-dependent roles for HMGB1 from different cellular compartments during infection. We provide mechanistic evidence that HMGB1 from circulating immune cells contributes to the timely induction of hepatic immune regulatory gene networks, early inflammatory monocyte recruitment to the liver and promotion of neutrophil survival, which are mandatory for pathogen control. In summary, our data establish HMGB1 as a critical co-factor in the immunological clearance of listeria, and argue against HMGB1 neutralization as a universal therapeutic strategy for sepsis.\n\nAuthor summaryHigh-mobility group box 1 (HMGB1) is an abundantly expressed nucleoprotein with signaling properties following secretion or release into the extracellular space. Given its central immune-regulatory roles during tissue injury and LPS-induced septic shock, interventions aimed at HMGB1 signaling have been advocated as therapeutic options for various disease conditions. Here, we show that antibody-mediated HMGB1 neutralization interferes with immunological defense against Listeria monocytogenes, a gram-positive bacterium with high pathogenic relevance for rodents and humans, effectuating uncontrolled bacterial growth and inflammation. Using conditional knockout animals, we demonstrate that while leukocyte functionality is preserved in HMGB1-deficient myeloid cells, HMGB1 released in response to Listeria triggers hepatic inflammatory monocyte recruitment and activation of transcriptional immune networks required for the early control of bacterial dissemination. Hepatocyte HMGB1, a key driver of post-necrotic inflammation in the liver, is dispensable for the immune response during moderately severe infection, but likely contributes to excessive hepatitis when infection is uncontrolled and cellular injury is high. We demonstrate a critical and non-redundant role for HMGB1 in the immune-mediated clearance of listeriosis and argue against HMGB1 neutralization as a universal therapeutic option in the context of infection.

immunology↗