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Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
MerTK is required for apoptotic cell-induced T cell tolerance
Mark A Wallet1, Pradip Sen, Rafael R Flores
1Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
The Journal of Experimental Medicine
|January 16, 2008
Summary
Self-antigens from apoptotic cells (ACs) can trigger autoimmunity. The MerTK receptor on dendritic cells (DCs) normally prevents this by inhibiting DC activation, but its absence exacerbates autoimmune diabetes.
Area of Science:
- Immunology
- Autoimmunity
- Cell biology
Background:
- Self-antigens from apoptotic cells (ACs) can initiate autoimmune responses.
- ACs possess an ability to inhibit antigen-presenting cells, like dendritic cells (DCs), contributing to self-tolerance.
- The precise mechanisms underlying AC-mediated inhibition of DCs remain incompletely understood.
Purpose of the Study:
- To investigate the role of the receptor tyrosine kinase Mer (MerTK) in mediating the inhibitory effects of ACs on DCs.
- To determine the impact of MerTK deficiency on the development and progression of autoimmune diabetes in a mouse model.
- To elucidate the contribution of MerTK to self-tolerance involving ACs, DCs, and T cells.
Main Methods:
- Dendritic cells (DCs) from nonobese diabetic (NOD) mice were pretreated with ACs.
- MerTK-deficient NOD mice (NOD.MerTK(KD/KD)) were utilized to assess the role of MerTK.
- Experimental autoimmune diabetes was induced, and immune cell populations and functions were analyzed.
Main Results:
- AC-induced inhibition of DC activation, cytokine secretion, and T cell stimulation was dependent on MerTK and its ligand Gas6.
- NOD.MerTK(KD/KD) mice exhibited exacerbated autoimmune diabetes compared to control NOD mice.
- Lack of MerTK led to increased activation and T cell stimulatory capacity of pancreatic DCs, promoting autoimmune responses.
Conclusions:
- MerTK is crucial for mediating the tolerance-inducing effects of ACs on DCs.
- MerTK deficiency impairs self-tolerance, leading to heightened autoimmune responses and exacerbated diabetes.
- These findings highlight MerTK as a key regulator in the interplay between ACs, DCs, and T cells for maintaining self-tolerance.
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