Presentation Title

Wound Repair and the Immune System in the Presence of Rapamycin

Faculty Mentor

Julie Jameson

Start Date

17-11-2018 10:00 AM

End Date

17-11-2018 10:15 AM

Location

C162

Session

Oral 2

Type of Presentation

Oral Talk

Subject Area

biological_agricultural_sciences

Abstract

The mammalian target of rapamycin, mTOR, plays a vital role in T cell metabolism, proliferation, and survival. While the ingestion of rapamycin and mTOR inhibition extends lifespan in mice, rapamycin can also cause immunosuppression leaving the organism susceptible to infection. Since barrier tissues such as the skin and intestine contain large populations of T cells that mediate protection and repair, epithelial tissues were analyzed to elucidate the impact of mTOR inhibition. Specifically, mice were fed a rapamycin-fortified diet ad libitum for ten weeks followed by the examination of tissue repair and T cell phenotyping. Epithelial T cells were quantified and analyzed through immunofluorescent microscopy and flow cytometry of intestinal and skin samples as compared to the spleen and thymus. The results from these experiments indicate that rapamycin affects T cell numbers in the thymus, CD4+ T cells in the spleen, and reduces the rate of epidermal wound healing. However, no significant difference between treatment and control groups was observed in the number of intraepithelial lymphocytes in the small intestine or skin. There do not appear to be histological changes in the villi or epidermis indicating that there are no direct impacts of mTOR suppression on epithelial cell homeostasis. The results from these experiments indicate that oral delivery of rapamycin impacts T cells differently depending on their location in the organism. However, the function of the T cell compartment in barrier tissues may be compromised as wound closure is delayed suggesting that use of rapamycin as an anti-aging therapy may have adverse effects. Future experiments will investigate the function of epithelial T cell populations to determine how rapamycin affects their ability to participate in epithelial repair.

Summary of research results to be presented

Mice fed a rapamycin-fortified diet exhibited a slower rate of wound healing compared to control mice. Epidermal gamma delta T cell number is not reduced in rapamycin-fed mice as compared to control mice. The number of CD4+ T cells in the spleen is decreased in the rapamycin-fed mice as compared to control mice. T cells are reduced in the thymus of rapamycin-fed mice. The number of CD3+ T cells in the villi of the small intestine did not change between control and rapamycin-fed mice.

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Nov 17th, 10:00 AM Nov 17th, 10:15 AM

Wound Repair and the Immune System in the Presence of Rapamycin

C162

The mammalian target of rapamycin, mTOR, plays a vital role in T cell metabolism, proliferation, and survival. While the ingestion of rapamycin and mTOR inhibition extends lifespan in mice, rapamycin can also cause immunosuppression leaving the organism susceptible to infection. Since barrier tissues such as the skin and intestine contain large populations of T cells that mediate protection and repair, epithelial tissues were analyzed to elucidate the impact of mTOR inhibition. Specifically, mice were fed a rapamycin-fortified diet ad libitum for ten weeks followed by the examination of tissue repair and T cell phenotyping. Epithelial T cells were quantified and analyzed through immunofluorescent microscopy and flow cytometry of intestinal and skin samples as compared to the spleen and thymus. The results from these experiments indicate that rapamycin affects T cell numbers in the thymus, CD4+ T cells in the spleen, and reduces the rate of epidermal wound healing. However, no significant difference between treatment and control groups was observed in the number of intraepithelial lymphocytes in the small intestine or skin. There do not appear to be histological changes in the villi or epidermis indicating that there are no direct impacts of mTOR suppression on epithelial cell homeostasis. The results from these experiments indicate that oral delivery of rapamycin impacts T cells differently depending on their location in the organism. However, the function of the T cell compartment in barrier tissues may be compromised as wound closure is delayed suggesting that use of rapamycin as an anti-aging therapy may have adverse effects. Future experiments will investigate the function of epithelial T cell populations to determine how rapamycin affects their ability to participate in epithelial repair.