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Antiinflammatory effects of CD95 ligand (FasL)-induced apoptosis
1Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Abstract:
Apoptosis is critical to homeostasis of multicellular organisms. In immune privileged sites such as the eye, CD95 ligand (FasL)-induced apoptosis controls dangerous inflammatory reactions that can cause blindness. Recently, we demonstrated that apoptotic cell death of inflammatory cells was a prerequisite for the induction of immune deviation after antigen presentation in the eye. In this report, we examine the mechanism by which this takes place. Our results show that Fas- mediated apoptosis of lymphoid cells leads to rapid production of interleukin (IL)-10 in these cells. The apoptotic cells containing IL-10 are responsible for the activation of immune deviation through interaction with antigen-presenting cells (APC). In support of this, we found that apoptotic cells from IL-10(+/+) animals fed to APC in vitro promote Th2 cell differentiation, whereas apoptotic IL-10(-/-) cells, as well as nonapoptotic cells, favor Th1 induction. Thus, apoptotic cell death and tolerance are linked through the production of an antiinflammatory cytokine to prevent dangerous and unwanted immune responses that might compromise organ integrity.
Insights
Apoptotic cells in the eye produce interleukin-10 (IL-10), a key anti-inflammatory cytokine. This IL-10 from dying cells promotes immune tolerance and prevents harmful inflammation, safeguarding organ integrity.
Area of Science:
- Immunology
- Cell Biology
- Ophthalmology
Background:
- Apoptosis is crucial for maintaining tissue homeostasis in multicellular organisms.
- In immune-privileged sites like the eye, CD95 ligand (FasL)-induced apoptosis prevents damaging inflammation that can lead to blindness.
- Previous studies showed apoptotic cell death is necessary for immune deviation induction in the eye.
Purpose of the Study:
- To investigate the mechanism by which apoptotic cell death induces immune deviation in the eye.
- To understand the role of cytokines in the process of Fas-mediated apoptosis and immune tolerance.
Main Methods:
- Examined the mechanism of Fas-mediated apoptosis in lymphoid cells within the eye.
- Measured the production of interleukin-10 (IL-10) in apoptotic lymphoid cells.
- Assessed the effect of apoptotic cells from IL-10(+/+) and IL-10(-/-) animals on antigen-presenting cells (APCs) and T helper (Th) cell differentiation in vitro.
Main Results:
- Fas-mediated apoptosis of lymphoid cells rapidly induces the production of IL-10.
- Apoptotic cells containing IL-10 activate immune deviation through interaction with APCs.
- In vitro, apoptotic cells from IL-10(+/+) animals promoted Th2 differentiation, while IL-10(-/-) apoptotic cells and nonapoptotic cells favored Th1 induction.
Conclusions:
- Apoptotic cell death is mechanistically linked to immune tolerance in the eye via IL-10 production.
- IL-10-producing apoptotic cells prevent potentially damaging immune responses, preserving ocular integrity.
- This pathway highlights a critical mechanism for controlling inflammation and maintaining immune privilege in the eye.