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Exploring the VISTA of microglia: immune checkpoints in CNS inflammation
Malte Borggrewe1, Susanne M Kooistra1, Randolph J Noelle2
1Department of Biomedical Sciences of Cells & Systems, Section Molecular Neurobiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract:
Negative checkpoint regulators (NCR) are intensely pursued as targets to modulate the immune response in cancer and autoimmunity. A large variety of NCR is expressed by central nervous system (CNS)-resident cell types and is associated with CNS homeostasis, interactions with peripheral immunity and CNS inflammation and disease. Immunotherapy blocking NCR affects the CNS as patients can develop neurological issues including encephalitis and multiple sclerosis (MS). How these treatments affect the CNS is incompletely understood, since expression and function of NCR in the CNS are only beginning to be unravelled. V-type immunoglobulin-like suppressor of T cell activation (VISTA) is an NCR that is expressed primarily in the haematopoietic system by myeloid and T cells. VISTA regulates T cell quiescence and activation and has a variety of functions in myeloid cells including efferocytosis, cytokine response and chemotaxis. In the CNS, VISTA is predominantly expressed by microglia and macrophages of the CNS. In this review, we summarize the role of NCR in the CNS during health and disease. We highlight expression of VISTA across cell types and CNS diseases and discuss the function of VISTA in microglia and during CNS ageing, inflammation and neurodegeneration. Understanding the role of VISTA and other NCR in the CNS is important considering the adverse effects of immunotherapy on the CNS, and in view of their therapeutic potential in CNS disease.
Insights
Negative checkpoint regulators (NCRs) modulate immune responses. V-type immunoglobulin-like suppressor of T cell activation (VISTA), an NCR, plays roles in CNS homeostasis and disease, impacting microglia and T cells.
Area of Science:
- Neuroimmunology
- Immunotherapy
- Cellular Immunology
Background:
- Negative checkpoint regulators (NCRs) are crucial for immune modulation in cancer and autoimmunity.
- NCRs are expressed in the central nervous system (CNS) and influence CNS homeostasis, inflammation, and disease.
- Immunotherapy targeting NCRs can lead to neurological side effects, indicating a need to understand their CNS roles.
Purpose of the Study:
- To review the role of NCRs in the CNS during health and disease.
- To highlight the expression and function of V-type immunoglobulin-like suppressor of T cell activation (VISTA) in the CNS.
- To discuss the therapeutic potential of NCRs in CNS disorders.
Main Methods:
- Literature review focusing on NCRs in the CNS.
- Analysis of VISTA expression in various CNS cell types and diseases.
- Discussion of VISTA's function in microglia and its involvement in CNS aging, inflammation, and neurodegeneration.
Main Results:
- VISTA is an NCR primarily expressed in the hematopoietic system by myeloid and T cells.
- VISTA regulates T cell activation and myeloid cell functions like efferocytosis and cytokine response.
- In the CNS, VISTA is predominantly expressed by microglia and macrophages.
Conclusions:
- Understanding NCRs, particularly VISTA, in the CNS is critical due to immunotherapy-related neurological adverse effects.
- VISTA's functions in microglia are important in CNS aging, inflammation, and neurodegeneration.
- NCRs hold therapeutic potential for treating CNS diseases.
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