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Publication Date

5-2025

Abstract

The cellular microenvironment is maintained by various homeostatic mechanisms, such as pH and temperature regulation. These factors can alter signaling and transcriptional activity in natural killer (NK) cells, significantly impacting their activation and function. These homeostatic mechanisms can be disrupted by factors such as infection or injury, such as within the tumor microenvironment. NK cells are essential for regulating the immune response by promoting and resolving inflammation to maintain tissue homeostasis. However, the mechanisms by which NK cells sense and respond to environmental factors, such as low pH or high heat, are not fully understood. In this study, we investigated the impact of inflammatory conditions (acid and heat) on human NK cells purified from the blood of healthy donors. NK cells were cultured in low pH (pH=6.5) and high temperature (40°C) environments. After 4 hours of culture, RNA was isolated from NK cells and underwent RNA sequencing and supernatant was harvested for cytokine analysis. We found that NK cells undergo specific gene alterations in response to inflammatory environments. These alterations influence the secretion of various cytokines and chemokines including GM-CSF, IFN-γ, Granzyme A, Granzyme B, MIP1-α, and sFasL. These findings indicate that NK cells utilize specific transcriptional regulatory mechanisms to influence tissue homeostasis. Understanding how NK cells respond to inflammation is crucial for comprehending their role in various diseases and their ability to recognize and respond to pathogens. Future studies will explore the temporal response of NK cells throughout the duration of an innate immune response.

Document Type

Poster

Transcriptional dynamics of natural killer cells under hyperthermic and acidic inflammatory conditions

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