KANSAS-NEBRASKA-OKLAHOMA The Protective Role of NKG2D in Type 1 Diabetes Autoimmunity

Overview

Over 12 million Americans live with Type 1 Diabetes (T1D), a debilitating autoimmune disease marked by insulitis of the pancreas and the destruction of beta-islet cells by effector Tcells (Teffs). The Markiewicz lab hypothesizes that expression of the immune receptor NKG2D is associated with an equilibrium between CD8+ regulatory Tcells (Tregs) and Teffs, creating balanced immune responses. Through single-cell RNA sequencing, the Markiewicz lab has identified the CD8+ Treg subset that inhibits diabetes to cells expressing the following surface markers: CD44, CD62L, and Ly49A. While CD4+ Tregs have been the focus of a majority of studies on T1D autoimmunity, the mechanism of CD8+ Tregs remains undetermined. We suggest that the absence of NKG2D will limit the proliferation of the aforementioned subpopulation in the non-obese diabetic (NOD) mouse model; to test this hypothesis, we harvested spleens, pancreatic lymph nodes, and axillary lymph nodes from NOD NKG2D wild-type (WT) and knockout (KO) mice. We then performed CD8+CD62L+ cell enrichments and flow cytometry analysis on these tissues. Contrary to our hypothesis, the spleens and pancreatic lymph nodes of the KO mice contained a significantly larger population of CD8+CD44+CD62L+Ly49A+ Tcells versus the WT mice, allowing us to conclude that NKG2D signaling does not enhance the proliferation of Ly49a+ Tregs in diabetes-associated tissues. These findings regarding NKG2D signaling and the proliferation of CD8+Ly49A+ Tregs will provide a greater background on NKG2D’s protective role in T1D and thus could provide therapeutic targets for the treatment of the disease.

Competition history

• JSHS 2022 Category not listed

Resources

• National JSHS abstract book ↗

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