Delineating the role of CXCR6 for the formation and maintenance of CD8+ tissue-resident memory T cells in the gut 2260742

Abstract

Abstract Introduction The CXCR6-CXCL16 axis has emerged as a critical regulator of T cell migration across various barrier tissues, thereby shaping localized immune memory. CXCR6 may help maintain the retention and function of CD8+ T cells in multiple tissues after infection, influencing not only immediate effector responses but also the long-term memory landscape of T cell populations. However, definitive in vivo data on the effect of CXCR6 on CD8+ T intraepithelial lymphocytes in the intestine (siIELs) are lacking. Methods Using the lymphocytic choriomeningitis virus (LCMV) Armstrong mouse model, we aim to examine the differential effects of CXCR6 deletion in the gut and identify the tissue-specific producers of the CXCR6 ligand, CXCL16. For this, we employ spectral flow cytometry and plan to use bulk and single-cell RNA sequencing, mass spectrometry imaging, and spatial transcriptomics. Results Preliminary adoptive transfer experiments showed that, when assessed in bulk, the ratio of CXCR6-deficient to wild-type P14 CD8+ T cells was lower among siIELs at day 7 after acute infection. Notably, within this population at the same time point, CXCR6 deficiency led to reduced CD69 expression and a reciprocal increase in CD103. Additionally, CD103+CD69+ KO CD8+ T cells were increased in the gut compared to adoptively transferred WT cells. Meanwhile, the expression of CD127 and KLRG1 remained unchanged. Conclusion Together, these findings suggest that CXCR6 plays a role in maintaining immune homeostasis and supporting the adaptive immune response in the gut during the early stages of acute infection. Funding Source In-institute funding. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)