Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with
Adi Vaknin-Dembinsky1, Gopal Murugaiyan, David A Hafler
1Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, USA.
Abstract:
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). In MS, myeloid dendritic cells (mDCs) secrete elevated amounts of IL-23, a potent proinflammatory cytokine, compared to healthy donors. Here, we examined the role of CD46, a complement binding factor, in mDCs by analyzing cytokine and chemokine production in healthy donors and patients with MS. There were striking differences between these groups with increased IL-23p19, CCL3 and CCL5 production, but decreased CCL2 levels in patients. This demonstrates major differences of DC activation upon CD46 activation, with a potential role in the pathogenesis of MS.
Insights
Myeloid dendritic cells (mDCs) in multiple sclerosis (MS) patients show altered cytokine production compared to healthy individuals. CD46 activation reveals distinct differences in mDC responses, potentially contributing to MS pathogenesis.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system (CNS) inflammatory disease.
- Myeloid dendritic cells (mDCs) from MS patients exhibit elevated Interleukin-23 (IL-23) secretion.
- CD46, a complement binding factor, is implicated in immune cell regulation.
Purpose of the Study:
- To investigate the role of CD46 activation in myeloid dendritic cell (mDC) function.
- To compare cytokine and chemokine production by mDCs from healthy donors and MS patients upon CD46 activation.
Main Methods:
- Analysis of cytokine and chemokine profiles in myeloid dendritic cells (mDCs).
- Comparison between healthy donors and patients with multiple sclerosis (MS).
- Focus on CD46 activation and its downstream effects on mDC signaling.
Main Results:
- Significant differences observed in mDC cytokine production between MS patients and healthy donors.
- Increased production of IL-23p19, CCL3, and CCL5 in MS patient mDCs.
- Decreased levels of CCL2 observed in mDCs from MS patients.
Conclusions:
- CD46 activation leads to distinct patterns of mDC activation in multiple sclerosis.
- Altered cytokine and chemokine profiles suggest a role for mDCs and CD46 in MS pathogenesis.
- These findings highlight potential therapeutic targets within DC pathways in MS.
