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The macrophage migration inhibitory factor pathway in human B cells is tightly controlled and dysregulated in multiple sclerosis
- Source :
- European Journal of Immunology, 48, 1861-1871, European Journal of Immunology, European Journal of Immunology, 48, 11, pp. 1861-1871, European Journal of Immunology, 48(11), 1861-1871. Wiley-VCH
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- In MS, B cells survive peripheral tolerance checkpoints to mediate local inflammation, but the underlying molecular mechanisms are relatively underexplored. In mice, the MIF pathway controls B‐cell development and the induction of EAE. Here, we found that MIF and MIF receptor CD74 are downregulated, while MIF receptor CXCR4 is upregulated in B cells from early onset MS patients. B cells were identified as the main immune subset in blood expressing MIF. Blocking of MIF and CD74 signaling in B cells triggered CXCR4 expression, and vice versa, with separate effects on their proinflammatory activity, proliferation, and sensitivity to Fas‐mediated apoptosis. This study reveals a new reciprocal negative regulation loop between CD74 and CXCR4 in human B cells. The disturbance of this loop during MS onset provides further insights into how pathogenic B cells survive peripheral tolerance checkpoints to mediate disease activity in MS.
- Subjects :
- Male
0301 basic medicine
CD74
Apoptosis
CXCR4
0302 clinical medicine
Autoimmune disease
Immunology and Allergy
B‐cell biology
B-Lymphocytes
Research Article|Clinical
Peripheral tolerance
Middle Aged
Women's cancers Radboud Institute for Health Sciences [Radboudumc 17]
Up-Regulation
Cell biology
Intramolecular Oxidoreductases
Immunodeficiencies and autoimmunity
Female
medicine.symptom
Research Article
Signal Transduction
Adult
Receptors, CXCR4
Multiple Sclerosis
Cell Survival
Immunology
Down-Regulation
chemical and pharmacologic phenomena
Inflammation
Biology
Proinflammatory cytokine
Clinical
Young Adult
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
Immune system
Downregulation and upregulation
otorhinolaryngologic diseases
medicine
Humans
Macrophage Migration-Inhibitory Factors
Aged
Cell Proliferation
Histocompatibility Antigens Class II
MIF receptors CXCR4/CD74
MS
Antigens, Differentiation, B-Lymphocyte
Clinically isolated syndrome
030104 developmental biology
Macrophage migration inhibitory factor
030215 immunology
Subjects
Details
- ISSN :
- 00142980
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- European Journal of Immunology
- Accession number :
- edsair.doi.dedup.....70a0aaaff9451f50063ce1a740fbb7d7