IL-10 mediates plasmacytosis-associated immunodeficiency by inhibiting complement-mediated neutrophil migration - 05/05/16
Abstract |
Background |
Plasmacytosis (ie, an expansion of plasma cell populations to much greater than the homeostatic level) occurs in the context of various immune disorders and plasma cell neoplasia. This condition is often associated with immunodeficiency that causes increased susceptibility to severe infections. Yet a causative link between plasmacytosis and immunodeficiency has not been established.
Objective |
Because recent studies have identified plasma cells as a relevant source of the immunosuppressive cytokine IL-10, we sought to investigate the role of IL-10 during conditions of polyclonal and neoplastic plasmacytosis for the regulation of immunity and its effect on inflammation and immunodeficiency.
Methods |
We used flow cytometry, IL-10 reporter (Vert-X) and B cell–specific IL-10 knockout mice, migration assays, and antibody-mediated IL-10 receptor blockade to study plasmacytosis-associated IL-10 expression and its effect on inflammation and Streptococcus pneumoniae infection in mice. ELISA was used to quantify IL-10 levels in patients with myeloma.
Results |
IL-10 production was a common feature of normal and neoplastic plasma cells in mice, and IL-10 levels increased with myeloma progression in patients. IL-10 directly inhibited neutrophil migration toward the anaphylatoxin C5a and suppressed neutrophil-dependent inflammation in a murine model of autoimmune disease. MOPC.315.BM murine myeloma leads to an increased incidence of bacterial infection in the airways, which was reversed after IL-10 receptor blockade.
Conclusion |
We provide evidence that plasmacytosis-associated overexpression of IL-10 inhibits neutrophil migration and neutrophil-mediated inflammation but also promotes immunodeficiency.
Le texte complet de cet article est disponible en PDF.Key words : Plasmacytosis, IL-10, immunodeficiency, neutrophil, inflammation
Abbreviations used : Foxp3, GFP, GMD, GST, IC, MM, SLE, Treg
Plan
| Supported by the Excellence Cluster “Inflammation at Interfaces,” the IRTG 1911, and the GRK1727. D.M.W. was supported by an internal program grant of the University of Lübeck. U.K. was supported by the priority program of the University of Lübeck “SPP-MIA.” F.D.F. is supported by the US Department of Veterans Affairs. K.B. received support from DFG-KFO 21. |
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| Disclosure of potential conflict of interest: U. Kulkarni receives travel support from The German Research Foundation. B. Tiburzy, L. Meng, R. J. Ludwig, K. Pollok, F. D. Finkelman, J. Köhl, and R. A. Manz receive research support from the German Research Foundation. T. Kamradt receives research support from Novartis Germany. C. Langer serves on the Advisory Board for Celegene, Janssen and Bristol-Myers Squibb. F. D. Finkelman is an Associate Editor of the Journal of Allergy and Clinical Immunology. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 5
P. 1487 - mai 2016 Retour au numéro
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