# Proinflammatory properties of Paneth cells in intestinal inflammation > **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $33,770 ## Abstract PROJECT SUMMARY Crohn's disease, a chronic inflammatory condition that most commonly affects the ileum, has an unclear but multifactorial etiology. The TnfΔARE/+ mouse model recapitulates features of ileal Crohn's disease and is driven by systemic overexpression of TNF, a proinflammatory cytokine that is elevated in Crohn's disease patients. The contribution of intestinal epithelial cell types to chronic, TNF-induced ileal inflammation is not known. Paneth cells are a type of intestinal epithelial cell that secrete antimicrobials to protect the epithelium from microbes that colonize the luminal compartment. It is hypothesized that impaired antimicrobial barrier function, due to Paneth cell defects and loss, contributes to the development of Crohn's disease. However, our preliminary data suggests that Paneth cells may have proinflammatory properties in chronic ileal inflammation, as Paneth cell ablation reverses ileal disease in TnfΔARE/+ mice. The hypothesis of this proposal is that Paneth cells have proinflammatory properties that drive ileal inflammation in the TnfΔARE/+ mouse model of Crohn's disease. Programmed cell death and autophagy are tightly regulated cellular processes that allow the tissue to manage aged or stressed cells. Although there is evidence that these processes may be dysregulated in Crohn's disease, there is no mechanistic evidence of proinflammatory Paneth cell death as a driver of chronic ileal inflammation. In Aim 1, single-cell technologies will be leveraged to investigate how specific mechanisms of Paneth cell death contribute to ileal inflammation the TnfΔARE/+ model. Experimental approaches include advanced Paneth cell ablation techniques, our multiplex immunofluorescence (MxIF) imaging pipeline, and transmission electron microscopy. Furthermore, mesenchymal cells, such as fibroblasts, are in close proximity to Paneth cells and epithelial-mesenchymal crosstalk is an established phenomenon in the intestine. Paneth cells express cytokines, such as TNF and IL- 17, and moreover, myofibroblasts are activated by epithelial-derived cytokines to promote an inflammatory cascade. However, Paneth cell-derived factors, such as cytokines, have not been associated with Crohn's disease, and furthermore, Paneth cell-mesenchymal cell interactions have not been established. In Aim 2, single- cell techniques will be leveraged to identify Paneth cell-derived proinflammatory cytokines, and computational methods will be used to determine if Paneth cell-mesenchymal cell interactions promote ileal inflammation. My approaches include single-cell RNA-sequencing, our computational cell-cell communication pipeline, and our MxIF imaging pipeline. I will also use mouse models to drive TNF overexpression from Paneth cells, and use in vitro approaches to determine whether Paneth cell-derived TNF directly activates fibroblasts. Revealing mechanisms by which Paneth cells drive ileal inflammation is critical for understanding Crohn's disease and will l... ## Key facts - **NIH application ID:** 10315219 - **Project number:** 1F31DK127687-01A1 - **Recipient organization:** VANDERBILT UNIVERSITY - **Principal Investigator:** Paige Nicole Spencer - **Activity code:** F31 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $33,770 - **Award type:** 1 - **Project period:** 2021-06-01 → 2024-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10315219 ## Citation > US National Institutes of Health, RePORTER application 10315219, Proinflammatory properties of Paneth cells in intestinal inflammation (1F31DK127687-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10315219. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*