Virginia Research Day 2025

Graduate Student Research Biomedical

02 Gut Microbiota Immunomodulations in CX 3 CR1 Deficient Lupus Mice

Rana Estaleen 1 ; David Oakland2; Razan Alajoleen1; Ran Lu1; Hilary Montano1; Pavly Amin3; Aida Shakeri3; Xin M. Luo1 * ; Christopher M. Reilly 1 ,4* Corresponding author: erana@vt.ed

1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech 2 Translational Biology, Medicine and Health Graduate Program, Virginia Tech 3 Department of Biological Sciences, College of Science, Virginia Tech 4 Department of Biomedical Sciences, Edward Via College of Osteopathic Medicine

The gut microbiota contributes to the health and disease of host and an imbalance of the gut microbiota is linked to systemic lupus erythematosus (SLE), which is an autoimmune disease where the immune system attacks its tissues and organs. CX 3 CR1 is a chemokine receptor that initiates intracellular signaling cascades responsible for modulating cellular activity, proliferation, and survival. CX 3 CR1 is expressed on various types of cells, including lymphocytes and myeloid cells. The absence of CX 3 CR1 compromises the integrity of the intestinal barrier and changes the gut microbiota composition. In this study, we hypothesized that CX 3 CR1

modulates lupus-associated disease through gut microbiota-mediated renal infiltration of T cells producing interleukin 17 (IL-17). We developed Cx3cr1 -deficient (KO) MRL/ lpr lupus-prone mice by backcrossing MRL/ lpr with B6/ Cx3cr1 gfp/gfp for 12 generations. We investigated the effects of the gut microbiota on glomerulonephritis in Cx3cr1 wildtype (WT) and KO MRL/ lpr mice by performing a co-housing experiment for twelve weeks. Mice eat other mice feces a process called coprophagy. To this extent, co-housing of mice will allow exchange of the microbiome between animals. We observed that

KO MRL/ lpr mice co-housed with WT mice had a significant reduction of proteinuria. In addition, in renal lymphocytes, there was a substantial reduction of T helper cells producing IL-17A in KO MRL/ lpr mice co-housed with WT mice, albeit no effect on IL-17F production. Furthermore, co-housing with WT mice moderately decreased naïve CD4 + T cells in KO MRL/ lpr mice. The introduction of KO microbiota in WT mice, on the other hand, induced the production of cytotoxic T cells in WT MRL/ lpr mice. Our findings suggest that the gut microbiota may influence different T cell subsets to exacerbate lupus in Cx3cr1 deficient MRL/ lpr mice.

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