EXPLORING THE CD40-CD40L AXIS: REGULATION OF TH2/TH17 CELL DIFFERENTIATION VIA STAT6 SIGNALING AND ITS IMPACT ON NEONATAL SEPSIS LUNG INJURY PROGRESSION, PHYSICAL FITNESS, AND MENTAL HEALTH

Abstract

Purpose: This study aims to dissect the role of the CD40/CD40L axis in mediating Th2/Th17 cell differentiation via STAT6 signaling and its subsequent impact on the progression of neonatal sepsis-induced lung injury. Moreover, it seeks to extend the understanding of how this axis influences physical fitness and mental health outcomes in the context of neonatal sepsis. Method: Utilizing a controlled experimental design, this research conducted cellular experiments and developed animal models to examine the expression of critical signaling molecules, cytokine secretion levels, and transcription factors. Key metrics such as cell proliferation, survival rates, migration, and invasion capabilities were assessed. Furthermore, the study analyzed the infiltration of inflammatory cells and the presence of sepsis-related factors in lung tissue. Result: The investigation identified a significant variance in the expression of IL-4R within the STAT6 signaling pathway between experimental and control groups, highlighting the pivotal role of this receptor in mediating immune responses. Although differences in the expression levels of TLR2/3 and IFN-γ were minimal, the activation of CD40/CD40L signaling was found to enhance Th2 cell division notably. Contrarily, the suppression of CD40/CD40L signaling appeared to diminish Th17 cell differentiation and IL-17 production, suggesting a potential pathway to mitigate inflammatory responses and tissue damage. Conclusion: Our findings underscore the critical function of the CD40/CD40L axis in regulating Th2/Th17 cell differentiation through STAT6 signaling, which significantly influences the progression of neonatal sepsis-induced lung injury. Activation of this axis promotes Th2 differentiation and IL-4 secretion, potentially exacerbating inflammatory responses and lung tissue damage. Conversely, inhibiting CD40/CD40L signaling may suppress Th17 differentiation and IL-17 production, offering a therapeutic avenue to alleviate inflammation and protect lung tissue. This study not only sheds light on the intricate immune mechanisms underlying neonatal sepsis but also suggests broader implications for physical fitness and mental health resilience in affected neonates, opening new vistas for integrated therapeutic strategies.