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Differential expression of CD11c by peripheral blood NK cells reflects temporal activity of multiple sclerosis
Toshimasa Aranami1, Sachiko Miyake, Takashi Yamamura
1Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Abstract:
Multiple sclerosis (MS) is an autoimmune disease, showing a great degree of variance in temporal disease activity. We have recently demonstrated that peripheral blood NK cells biased for secreting IL-5 (NK2 bias) are associated with the remission state of MS. In this study, we report that MS patients in remission differentially express CD11c on NK cell surface (operationally defined as CD11chigh or CD11clow). When we compared CD11chigh or CD11clow patients, the expression of IL-5 and GATA-3 in NK cells supposed to endow a disease-protective NK2 phenotype was observed in CD11clow but not in CD11chigh patients. In contrast, the CD11chigh group showed a higher expression of HLA-DR on NK cells. In vitro studies demonstrated that NK cell stimulatory cytokines such as IL-15 would up-regulate CD11c expression on NK cells. Given previous evidence showing an association between an increased level of proinflammatory cytokines and temporal disease activity in MS, we postulate that inflammatory signals may play a role in inducing the CD11chigh NK cell phenotype. Follow-up of a new cohort of patients showed that 6 of 10 CD11chigh MS patients developed a clinical relapse within 120 days after evaluation, whereas only 2 of 13 CD11clow developed exacerbated disease (p = 0.003). As such, a higher expression of CD11c on NK cells may reflect the temporal activity of MS as well as a loss of regulatory NK2 phenotype, which may allow us to use it as a potential biomarker to monitor the immunological status of MS patients.
Insights
Natural killer (NK) cells expressing high levels of CD11c are linked to active multiple sclerosis (MS). Lower CD11c expression on NK cells correlates with disease remission, suggesting CD11c as a potential biomarker for MS activity.
Area of Science:
- Immunology
- Neuroimmunology
- Autoimmune Diseases
Background:
- Multiple sclerosis (MS) is a variable autoimmune disease.
- Peripheral blood NK cells with an IL-5 secreting bias (NK2 bias) are linked to MS remission.
- NK cell surface CD11c expression varies in MS patients.
Purpose of the Study:
- To investigate the differential expression of CD11c on NK cells in MS patients.
- To correlate CD11c expression levels with disease activity and NK cell phenotype.
- To evaluate CD11c as a potential biomarker for MS temporal activity.
Main Methods:
- Flow cytometry analysis of CD11c and HLA-DR expression on NK cells.
- Comparison of IL-5 and GATA-3 expression in CD11chigh and CD11clow NK cell subsets.
- In vitro studies with IL-15 stimulation of NK cells.
- Prospective follow-up of MS patients to assess clinical relapse rates.
Main Results:
- MS patients were categorized into CD11chigh and CD11clow NK cell groups.
- The CD11clow group showed higher IL-5 and GATA-3 expression, indicative of an NK2 phenotype.
- The CD11chigh group exhibited increased HLA-DR expression on NK cells.
- In vitro IL-15 stimulation increased NK cell CD11c expression.
- CD11chigh MS patients had a significantly higher rate of clinical relapse within 120 days (6/10) compared to CD11clow patients (2/13).
Conclusions:
- High CD11c expression on NK cells in MS patients may indicate increased disease activity and a loss of the protective NK2 phenotype.
- CD11c expression on NK cells could serve as a potential biomarker for monitoring MS immunological status and predicting relapse.
- Inflammatory signals may induce the CD11chigh NK cell phenotype in MS.
