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Updated: Dec 22, 2025
Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
MOSPD2 is a therapeutic target for the treatment of CNS inflammation
Abstract:
In multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), myeloid cells comprise a major part of the inflammatory infiltrate in the central nervous system (CNS). We previously described that motile sperm domain-containing protein 2 (MOSPD2) is expressed on human myeloid cells and regulates monocyte migration in vitro. The role of MOSPD2 in EAE pathogenesis was studied by generating MOSPD2 knock-out (KO) mice and monoclonal antibodies directed against MOSPD2. We found that EAE development in MOSPD2 KO mice was significantly suppressed. While frequency representation of leukocyte subsets in lymphoid tissues was comparable, the ratio of inflammatory monocytes in the blood was markedly reduced in MOSPD2 KO mice. In addition, T cells from MOSPD2 KO mice displayed reduced secretion of proinflammatory cytokines and increased production of interleukin (IL)-4. Prophylactic and post-onset treatment using monoclonal antibodies (mAbs) generated against MOSPD2 abrogated development and reduced EAE severity. These results suggest that MOSPD2 is key in regulating migration of inflammatory monocytes, and that anti-MOSPD2 mAbs constitute a potential therapy for the treatment of CNS inflammatory diseases.
Insights
Motile sperm domain-containing protein 2 (MOSPD2) regulates inflammatory monocyte migration. Blocking MOSPD2 suppressed experimental autoimmune encephalomyelitis (EAE) in mice, suggesting anti-MOSPD2 antibodies as a potential therapy for central nervous system (CNS) inflammatory diseases.
Area of Science:
- Neuroimmunology
- Inflammatory diseases
- Cellular and Molecular Immunology
Background:
- Myeloid cells are key inflammatory infiltrates in the central nervous system (CNS) in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE).
- Motile sperm domain-containing protein 2 (MOSPD2) is expressed on human myeloid cells and influences monocyte migration in vitro.
Purpose of the Study:
- To investigate the role of MOSPD2 in the pathogenesis of EAE.
- To evaluate the therapeutic potential of targeting MOSPD2 in CNS inflammatory diseases.
Main Methods:
- Generation of MOSPD2 knock-out (KO) mice.
- Development of monoclonal antibodies (mAbs) against MOSPD2.
- Assessment of EAE development and severity in MOSPD2 KO mice.
- Analysis of leukocyte subsets, monocyte ratios, and T cell cytokine production.
- Evaluation of prophylactic and therapeutic efficacy of anti-MOSPD2 mAbs in EAE.
Main Results:
- MOSPD2 KO mice exhibited significantly suppressed EAE development.
- A reduced ratio of inflammatory monocytes was observed in the blood of MOSPD2 KO mice.
- T cells from MOSPD2 KO mice showed reduced pro-inflammatory cytokine secretion and increased IL-4 production.
- Anti-MOSPD2 mAbs abrogated EAE development and reduced disease severity.
Conclusions:
- MOSPD2 plays a critical role in regulating inflammatory monocyte migration.
- Targeting MOSPD2 with monoclonal antibodies presents a promising therapeutic strategy for CNS inflammatory diseases like EAE.
