Immune deficiencies, infection, and systemic immune disordersIL-10 mediates plasmacytosis-associated immunodeficiency by inhibiting complement-mediated neutrophil migration
Section snippets
Mice
C57BL/6 and BALB/c mice were purchased from Charles River (Bar Harbor, Me). IL-10 reporter (Vert-X), BALB/c forkhead box protein 3 (Foxp3) reporter (Foxp3eGFP), and CD19 Cre/IL-10 flox/flox mice and their littermate controls were bred at the animal facility of the University of Lübeck. Experiments were performed at the animal facilities of the Universities of Lübeck and Greifswald.
Experimental epidermolysis bullosa acquisita and polyclonal plasmacytosis
Epidermolysis bullosa acquisita was induced by means of subcutaneous immunization and scored, as previously
Polyclonal and neoplastic plasmacytosis is associated with increased IL-10 production
B lineage cells with a CD138hi plasma cell/plasmablast phenotype can significantly contribute to IL-10 production and thereby control T cell–mediated autoimmune inflammation.28 Here, we first tested the possibility that plasmacytosis increases production of immunosuppressive IL-10. This cytokine was detectable in sera from 6 of 8 patients with advanced myeloma. In contrast, it was present only at a relatively low level in 1 of 7 healthy control subjects and undetectable in patients exhibiting
Discussion
Recent studies identified plasma cells as a relevant source of IL-10 that can control T cell–mediated inflammation.27, 28 The present study extends these findings and demonstrates that polyclonal and neoplastic plasmacytosis-associated IL-10 mediates suppression of effective neutrophil function. Even moderate GMD-induced polyclonal plasmacytosis was sufficient to block neutrophil-mediated inflammation and pathophysiology in an autoimmune setting, whereas neutrophil migration was completely
References (69)
- et al.
Plasma cell differentiation and survival
Curr Opin Immunol
(2008) - et al.
Stromal niches, plasma cell differentiation and survival
Curr Opin Immunol
(2006) - et al.
Rotavirus infection in adult small intestine allografts: a clinicopathological study of a cohort of 23 patients
Am J Transplant
(2010) - et al.
Mechanism of hypergammaglobulinemia by HIV infection: circulating memory B-cell reduction with plasmacytosis
Clin Immunol
(2001) - et al.
High incidence of peripheral blood plasmacytosis in patients with dengue virus infection
Clin Microbiol Infect
(2011) - et al.
Pathological findings in human autoimmune lymphoproliferative syndrome
Am J Pathol
(1998) - et al.
Infections in patients with multiple myeloma
Semin Hematol
(2009) - et al.
Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus
Trends Mol Med
(2012) Infectious diseases in systemic lupus erythematosus: risk factors, management and prophylaxis
Best Pract Res Clin Rheumatol
(2002)- et al.
Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation
Immunity
(2014)
Three different neutrophil subsets exhibited in mice with different susceptibilities to infection by methicillin-resistant Staphylococcus aureus
Immunity
Neutrophils come of age in chronic inflammation
Curr Opin Immunol
The immunoglobulin, IgG Fc receptor and complement triangle in autoimmune diseases
Immunobiology
Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow
Blood
Generation of antibodies of distinct subclasses and specificity is linked to H2s in an active mouse model of epidermolysis bullosa acquisita
J Invest Dermatol
Mechanisms that determine plasma cell lifespan and the duration of humoral immunity
Immunol Rev
Long-lived autoreactive plasma cells drive persistent autoimmune inflammation
Nat Rev Rheumatol
Maintenance of serum antibody levels
Annu Rev Immunol
Regulation of plasma-cell development
Nat Rev Immunol
Systemic lupus erythematosus and Castleman's disease
J Rheumatol
Bone marrow findings in patients with autoimmune liver diseases
J Gastroenterol Hepatol
Bone marrow abnormalities in systemic lupus erythematosus with peripheral cytopenia
Clin Exp Rheumatol
Pathogenesis of myeloma
Annu Rev Pathol
Molecular pathogenesis of multiple myeloma and its premalignant precursor
J Clin Invest
Polyclonal immune activation and marrow plasmacytosis in multiple myeloma patients receiving long-term lenalidomide therapy: incidence and prognostic significance
Leukemia
Multiple myeloma presenting with an acute bacterial infection
Int J Lab Hematol
Immunodeficiency and immunotherapy in multiple myeloma
Br J Haematol
Prophylactic use of antibiotics and immunisations in patients with SLE
Ann Rheum Dis
Diseases associated with immunosuppression
Environ Health Perspect
Infections and SLE
Autoimmunity
Plasma cells negatively regulate the follicular helper T cell program
Nat Immunol
Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORgammat and Ahr that leads to IL-17 production by activated B cells
Nat Immunol
IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases
Nature
IL-10 in myeloma cells
Leuk Lymphoma
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2021, Pharmacology and TherapeuticsCitation Excerpt :Members of the IL-10 family can also activate downstream molecules in addition to JAK-STAT, inhibit the production of pro-inflammatory cytokines and reduce the function of antigen-presenting cells (Ouyang & O'Garra, 2019). Moreover, IL-10 overexpression inhibits neutrophil migration and neutrophil-mediated inflammation (Kulkarni et al., 2016). Lara Campana et al. found that the STAT3-IL-10-IL-6 axis is a positive regulator of macrophage phagocytosis, survival and phenotypic transformation, which enhances the ability of macrophages to dispose of apoptotic bodies, thereby reducing inflammation and liver damage (Campana et al., 2018).
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2021, Journal of Investigative DermatologyCitation Excerpt :Details are found in Supplementary Materials and Methods. Antigen-specific plasma cells were stained with antigen, as previously described (Kulkarni et al., 2016; Tiburzy et al., 2013). Antigen-specific T cells were analyzed by the rapid antigen-induced upregulation of CD154 (Frentsch et al., 2005; Tiburzy et al., 2013).
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.
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.