Biology subjects

Franck, G.

Publications and source records attributed to Franck, G..

4 recordsLinked to original sources

bioRxiv2026

Fever-range temperature enhances B cells in vitro but is dispensable for the germinal center in vivo

Fever is a conserved physiological response to immune activation characterized by elevated body temperature. While hyperthermia enhances innate and T cell immunity, its role in shaping the B cell compartment remains poorly defined, despite B cells' role in long-term protection. Understanding how temperature modulates B cell physiology is relevant to vaccine strategies, particularly fever management around immunization. Therefore, we investigated the influence of fever-range thermal changes on humoral immunity. To decipher the direct effects, primary B cells from C57BL/6 mice were stimulated in vitro under mild hyperthermic conditions (~1.5{degrees}C increase). Fever-range temperature enhanced B cell activation, facilitated entry into cell division, and increased antigen presentation to CD4+ T cells, while transcriptomic analysis revealed enrichment of pathways involved in protein synthesis and mitochondrial respiration. To determine whether these intrinsic effects translated into altered humoral immunity in vivo, we developed a novel tunable implant-based system to induce localized, 48-hour hyperthermia around a draining lymph node in awake mice without altering core body temperature. Following subcutaneous NP-OVA/alum immunization, localized hyperthermia localized hyperthermia did not enhance antigen-specific germinal center B cell expansion, antibody titers or IgG affinity on day 9. Moreover, heating during priming did not affect the recall humoral response after a booster on day 21. Thus, fever-range temperature directly modulates murine B cell function in vitro but does not enhance humoral immunity in vivo, indicating that the biological consequences of intrinsic B cell thermosensitivity depend on its integration within the multicellular and inflammatory signals shaping germinal center responses.

immunology↗

bioRxiv2024

Inositol-Requiring Enzyme 1 Pathway and Autophagy Drive Sequential Response of Endothelial Cells to Febrile Range Hyperthermia

ContextFever is an evolutionarily conserved and adaptive response during infections. However, prolonged fever has numerous systemic metabolic and functional side effects. In the heart, prolonged fever associated with infection is linked to fatal adverse effects, particularly involving impaired coronary circulation. Yet, the direct relationship between elevated temperature and coronary microcirculation dysfunction, remains to be fully demonstrated. In this study, we aimed to explore the specific responses of human coronary artery endothelial cells (HCAECs) to fever-range hyperthermia. MethodHCAECs were cultured at either 37{degrees}C or 40{degrees}C for up to 24 hours. Transcriptomic and proteomic profiles were obtained through microarray and mass spectrometry after 6, 12, and 24 hours of exposure. Key signaling pathways, upstream regulators, and candidate mechanisms were identified and validated at the mRNA and protein levels using mechanistic approaches. ResultsProlonged hyperthermia compromised HCAEC function, evidenced by cell detachment, loss of junctions, and increased permeability. HCAECs rapidly activated the unfolded protein response (UPR), including IRE1 activation and XBP1 splicing. Additionally, autophagic flux was significantly elevated, participating in the degradation of junction proteins. Pharmacological inhibition of IRE1 reduced the autophagic burden, protected against cell detachment, and preserved junction integrity over time. ConclusionOur findings reveal that in response to fever-range hyperthermia, the IRE1-autophagy axis regulates the survival and function of coronary endothelial cells. This mechanism could play a key role in modulating endothelial responses during infection and contribute to the pathological outcomes of fever. Furthermore, it may be relevant in local inflammatory conditions with elevated temperatures.

cell biology↗

bioRxiv2023

Prolonged body temperature tuning in mice using radio frequency generating electromagnetic resonant circuit-system

RationalIn endothermic animals, body temperature (BT) is an evolutionary conserved and well characterized physical parameter that guarantees physiological functioning state. It results from the sum of bioenergetic processes of the body weighted by behavioral strategies, heat loss, and thermolytic processes. However, the intrinsic impact of temperature and temperature changes on the biology is far less understood. To date, the modification of the environmental temperature has constituted the main lever to evaluate the impact of thermic changes in small animal. However, studying intrinsic effect of temperature remains impossible using conventional laboratory equipment, mainly because hypothalamus instructed with information grabbed from the environmental temperature finely regulates and maintain body temperature around 37{degrees}C. Numerous pharmacological treatments have been used to block these thermoregulatory mechanisms, but confer high toxicity while dysregulating the central nervous responses and can potentially have confounding direct effects on studied peripheral tissues. Alternatively, physical methods using energy irradiation were reported, but they remain expensive and usually involve animal immobilization. We aimed at designing a simple and affordable device to adjust and maintain body temperature on the long course in conscious and free-moving animals. MethodWe developed an electromagnetic LC resonant circuit (ELM circuit) producing a radio frequency signal (64 kHz) inside a copper coil refrigerated with a water circuit. This setting is powered by a simple a 0-48V AC generator, allowing the use of a domestic electrical network. This setting can accommodate metal-free 3D-printed circular cages, where adult mice, previously implanted with thermometric ID transponders, are monitored remotely for intraperitoneal temperature over time. ResultsThe BT of mice placed in the ELM circuit could be regulated in a reproducible fashion. Healthy mice increased their BT from 37 to 39.8{+/-}1{degrees}C, upon power supply ranging from 0 to 48V, respectively. In septic mice developing hypothermia (33{+/-}1 {degrees}C), BT could be either normalized to normothermia (37{degrees}C, 24V), or increased to fever-range hyperthermia (40{degrees}C, 48V) as a function of radiofrequency energy. BT tuning was accurate and stable for at least 12h. Blood count after 6 or 12 hours showed no modifications between groups, cardiomyocyte displayed heat shock response within the first hour in mice exposed to the maximal dose (BT=41{degrees}C). MALDI TOF imaging on brain microsections revealed modifications of the brain proteome, as suggested by differential PKC-theta, and prolactin 7B1 load in heated mice, as compared to controls. ConclusionPrecise body temperature tuning is achievable in small animals, and could be of high interest to understand the impact of temperature in (patho)physiology.

physiology↗

bioRxiv2023

Opposing Strain Directions on Adjacent Left Ventricular Segments Predict Fibrotic Remodeling after Acute Myocardial Infarction

BackgroundDespite similar levels of coronary occlusion and standard of care management, the occurrence of scarring over adaptive heart repair following acute myocardial infarction (AMI) remains unpredictable. Recent studies indicate that mechanical cues may modulate the transcriptional programs involved in tissue repair, possibly explaining why ventricular mechanical dyssynchrony an independent predictor of post-infarction outcome. ObjectiveOur study aimed to investigate the relationship between mechanical cues and the outcome of post-myocardial infarction heart remodeling by live imaging. Specifically, we examined the impact of individual variability of myocardial dyssynchrony, characterized by a divergent direction of injured left ventricle wall movement next to live tissue, on the formation of a large scar, dilation of the left ventricle, and loss of pumping function. MethodsWe assessed the location and degree of regional systolic and diastolic dyssynchrony using transthoracic echocardiography coupled with speckle tracking imaging. Specifically, we measured the difference in absolute strain values between adjacent regions of the left ventricle at 5 days following the induction of a standard experimental infarction in female C57Bl6 mice. Three weeks later, transthoracic echocardiography was repeated to analyze the mass and global function of the left ventricle right before termination. We then examined the size of the scar in matched mid-sections of the left ventricle circumferential segments from each mouse using histomorphometry. Finally, we evaluated the potential impact on transcriptional tissue repair programs using spatial transcriptomic analysis on representative hearts with either adaptive or fibrotic post-infarction heart remodeling. ResultsWe analyzed all 96 systolic and diastolic strain-related parameters in the same 48 regions of the left ventricle in all mice, with echocardiographic and histological sections following the same orientation. Stepwise analysis of the live imaging data revealed that a combination of 8 regional strain parameters could predict fibrotic remodeling (Area under the ROC curve= 0.8290). We observed that scarring remodeling was associated with opposing trends of systolic and diastolic circumferential strain % delta values on adjacent regions at day 5, while adaptive remodeling at day 28 occurred when the trend followed the direction of control (sham) hearts. Cluster analysis of gene transcripts and speckle tracking assessment on representative hearts with adaptive or fibrotic post-infarction remodeling indicated a correlation between regional post-infarction dyssynchrony and the transcriptional program. Adrenergic receptors, including Adra1, Trpc3, and Myh7, were found to be linked to specific regional dyssynchrony values and scarring remodeling. ConclusionOur study demonstrates the potential of regional strain parameters obtained through live imaging in predicting fibrotic remodeling following myocardial infarction. Furthermore, our findings suggest a link between regional post-infarction dyssynchrony and the transcriptional program. These results highlight the potential applicability of our approach in clinical settings and provide insights for future personalization of therapeutic strategies.

physiology↗