Impacto da deficiência do receptor de quimiocina CXCR6 na resposta hepática a infecções

Abstract

The liver plays a fundamental role in the organism's homeostasis, not only in metabolic functions but also in immunological ones. It harbors numerous immune cells, with Natural Killer T (NKT) cells standing out for their highest proportion compared to other body tissues. These cells combine features of both T cells and NK cells, expressing typical surface receptors of these cell types. NKT cells exhibit differential receptor expression according to tissues or sites of inflammation, notably expressing CXCR6 in the liver. In this context, the present study aimed to understand the role of the chemokine receptor CXCR6 in the liver. To achieve this, animals with the CXCR6GFP/GFP genotype, homozygous and heterozygous, as well as wild-type (WT) animals, were used. The dynamics of CXCR6+ cells were evaluated throughout life using intravital confocal microscopy analysis, revealing that adult mice have fewer CXCR6+ cells per field, which migrate along hepatic sinusoids. In contrast, neonates showed a greater number of stationary cells. Additionally, hepatic immune response in the absence of CXCR6 was evaluated using an E. coli infection model. Comparatively, WT mice exhibited a more severe reaction to infection, whereas CXCR6-depleted animals displayed a milder response, assessed through mortality rates, clinical aspects, weight variation, and quantification of colony-forming units in the liver. Intravital confocal microscopy showed that the absence of the CXCR6 receptor resulted in less expansion of GFP+ cells over time compared to animals with the receptor. These findings provide significant insights into how the CXCR6 receptor influences infection response. Its absence appears associated with a less inflammatory and less damaging state to the mouse liver. Understanding these mechanisms may offer new therapeutic perspectives for managing inflammatory and infectious liver diseases, contributing to significant advances in clinical practice.