Characterization of a Novel Macrophage Population with a Protective Potential Against Immune Attack in T1D
Type 1 Diabetes (T1D) is an autoimmune disease that is characterized by insulin deficiency caused by specific destruction of pancreatic β-cells. The defects in the immune system that initiate the attack upon β-cells are unknown, and scarcity of human samples hampers analysis of the pre-diabetic pancreas. The Non-Obese Diabetic (NOD) mouse develops spontaneous autoimmune diabetes with genetic and environmental features similar to the human disease, and is therefore a powerful tool to study the origins of T1D. An intriguing feature of the immune attack in both mouse and humans may hold the potential to reveal the origins of T1D: The attack is asynchronous, so that infiltrated Islets and intact islets are often seen in close proximity.
In order to characterize the cellular composition of each configuration, we performed single-cell RNA sequencing of attacked and non-attacked islets from NOD mice, and characterized the cell population in each. While attacked islets harbor a plethora of immune cells, we identified a distinct population of macrophages with anti-inflammatory properties in the non-attacked islets. Through combined RNA-FISH and immunofluorescence, we found that these cells are present in the beginning of the immune attack, disappear when the immune attack is at its’ peak and reappear at the end of it. In addition, we have also identified a similar population in the human pancreas with different expression patterns between healthy, T1D and T2D patients. These observations suggest that these macrophages are a dynamic population of cells that are influenced by the current status of the immune attack and change accordingly.
Exploring the dynamics and properties of this interesting population could aid in gaining a better understanding of the complex “battlefield” of T1D.