Single-Cell RNA Sequencing in Pediatric Sepsis: γδ T Cell Exhibits a Differentiation to γδT17 Subtype along with Significantly Enhanced Cell Communication with Neutrophils.

UNLABELLED: <p>Introduction: Abnormal immune responses are common clinical features in septic patients. γδ T cells, as innate immune cells, play an important role in host defense, immune surveillance, and homeostasis. However, the immune characteristics of γδ T cells in pediatric sepsis remain poorly understood.

METHODS: In this study, we analyzed single-cell RNA high-throughput sequencing data of peripheral blood mononuclear cells from pediatric septic patients.

RESULTS: It demonstrates that γδ T cells exhibit a pro-inflammatory state with heightened immune responsiveness to pathogens in pediatric sepsis, as confirmed by the results of flow cytometric analysis showing elevated Th1 cytokine secretion, increased activation, and a propensity to differentiate into IL-17-producing (γδT17) cells during disease progression. Pseudotime analysis identified seven key genes potentially regulating the differentiation of γδ T cells to γδT17 subtype. Furthermore, cell-cell communication analysis revealed enhanced RETN-CAP1 binding between neutrophils and γδ T cells in pediatric sepsis, suggesting that neutrophil-derived resistin may promote γδ T-cell differentiation into the γδT17 subtype via CAP1 receptor binding.

CONCLUSION: This study presents analysis of a single-cell study on the immune status of γδ T cells in pediatric sepsis, highlighting their pivotal roles in pathogen response, inflammation propagation, and immune regulation. The observed differentiation toward the γδT17 subtype may facilitate neutrophil recruitment in this life-threatening condition. Elucidating the molecular mechanisms of γδ T cells in pediatric sepsis could offer a new theoretical basis for novel therapeutics. </p>.