| Title: |
Mononuclear phagocytes in autoimmune neuroinflammation. |
| Authors: |
Gogoleva, Violetta S.1 (AUTHOR), Mundt, Sarah1 (AUTHOR), De Feo, Donatella1 (AUTHOR), Becher, Burkhard1 (AUTHOR) becher@immunology.uzh.ch |
| Source: |
Trends in Immunology. Oct2024, Vol. 45 Issue 10, p814-823. 10p. |
| Subject Terms: |
*MACROPHAGES, *RETICULO-endothelial system, *BONE marrow, *CENTRAL nervous system, *PHAGOCYTES |
| Abstract: |
The development of novel conditional gene targeting tools is allowing us to disentangle the contribution of mononuclear phagocytes to autoimmune neuroinflammation. Microglia and border-associated macrophages are not major contributors to tissue damage but are involved in controlling inflammation and promoting tissue repair (remyelination) during experimental autoimmune encephalomyelitis, a mouse model for multiple sclerosis. Conventional dendritic cells play a dual role: they maintain tolerance to central nervous system (CNS) antigens while also facilitating the reactivation and expansion of pathogenic effector T cells within the CNS. Monocyte-derived macrophages can mediate tissue damage, although emerging evidence suggests that they may also possess tissue-protective and immunoregulatory properties. With emerging single-cell technologies and conditional gene targeting, it is evident that mammalian central nervous system (CNS)-associated phagocytes play crucial yet different and even opposing roles in neuroinflammation. Our developing understanding of their individual impact can help guide the development of more specific, effective, and safe therapies for patients suffering from neuroinflammatory diseases. A healthy mammalian central nervous system (CNS) harbors a diverse population of leukocytes including members of the mononuclear phagocyte system (MPS). Exerting their specific functions, CNS tissue-resident macrophages as well as associated monocytes and dendritic cells (DCs) maintain CNS homeostasis. Under neuroinflammatory conditions, leukocytes from the systemic immune compartment invade the CNS. This review focuses on the newly discovered roles of the MPS in autoimmune neuroinflammation elicited by encephalitogenic T cells. We propose that CNS-associated DCs act as gatekeepers and antigen-presenting cells that guide the adaptive immune response while bone marrow (BM)-derived monocytes contribute to immunopathology and tissue damage. By contrast, CNS-resident macrophages primarily support tissue function and promote the repair and maintenance of CNS functions. [ABSTRACT FROM AUTHOR] |
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