Basophils and Systemic Lupus Erythematosus in Murine Models and Human Patients (original) (raw)
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Basophils and Autoreactive IgE in the Pathogenesis of Systemic Lupus Erythematosus
Current Allergy and Asthma Reports, 2011
A hallmark of this disease, like for other autoimmune diseases, is the presence of large amounts of autoantibodies. As such SLE is considered to be a B cell disease perpetuated by the expansion of autoreactive T and B cells. The T cells involved have long been considered to be Th1 and Th17 cells as these potent pro-inflammatory cells can be found in the tissues of SLE patients.
Activated basophils give lupus a booster shot
Nature Medicine, 2010
Basophils have recently been identified as antigen-presenting cells that are required for optimal antibody responses. New findings now show that activation of these cells can amplify autoimmune responses in systemic lupus erythematosus (SLE).
Frontiers in Immunology
Tissue-specific mouse models are essential tools to decipher the role of each cell compartment and/or their expressed genes in the pathophysiology of diseases. Here, we describe a new knock-in mouse model allowing expression of both the fluorescent protein tdTomato and the CRE recombinase selectively in the basophil compartment under the control of the Mcpt8 gene. These “CT-M8” mice did not show any abnormalities in their peripheral distribution of major immune cell populations nor their basophil function. CT-M8 mice allowed the identification of basophils by immunofluorescence and flow cytometry and basophil-specific Cre-mediated floxed gene deletion. Breeding of our CT-M8 mice with the ROSA26flox-stop-DTA mice led to the generation of basophil-deficient mice with no detectable abnormalities in other cell compartments. These mice were then used to document basophil involvement in systemic lupus erythematosus (SLE) pathophysiology since we previously reported by transient depletion ...
Basophils and IgE: Linking the Allergic Environment to Autoimmunity
The Open Allergy Journal, 2010
As outlined in some of the accompanying articles in this issue, the role of the basophil as an effector cell in allergy and in host defense (particularly to parasites) has long been recognized. However, recent advances advocate for the basophil as an immunomodulatory cell that can promote naïve CD4 + T cell commitment to Th2 cell differentiation. While this is in keeping with the concept that the basophil is important in an allergic environment, new discoveries suggest that basophils may be immunomodulatory beyond the context of allergic disease. Here we mainly discuss our own work, which provides a new paradigm for the role of basophils beyond allergy. Our findings demonstrate the importance of autoreactive IgE's, IL-4 and basophils in promoting autoantibody production and the development of lupus nephritis. The conclusions drawn are based on studies in a mouse model (Lyn -/mice) of spontaneous systemic lupus erythematosus (SLE)-like disease as well as from analysis of the relationship between disease activity in SLE patients and their levels of autoreactive IgE's and activated basophils with antigen presenting capability. The findings demonstrate a link between the Th2 environment and autoimmunity and provide new areas of investigation with therapeutic potential.
Basophils, IgE, and Autoantibody-Mediated Kidney Disease
The Journal of Immunology, 2011
Basophils are of interest in immunology due to their ability to produce a Th2-signature cytokine, IL-4, following activation. A new understanding of the role of basophils in immunity shows novel functions at a cellular level through which basophils influence adaptive immunity. This review summarizes new advances in basophil biology and discusses new roles for basophils in human disease, especially in the mediation of the pathogenesis of lupus nephritis. Recently, basophils have been shown to contribute to self-reactive Ab production in systemic lupus erythematosus and may enhance pre-existing loss of B cell tolerance, suggesting that basophils, IL-4, and IgE mediate the pathogenesis of lupus nephritis by promoting the Th2 environment and activating autoreactive B cells. In addition to envisaging exciting therapeutic prospects, these novel findings open the way for the study of basophils in other autoimmune and renal diseases.
Basophils contribute to pristane-induced Lupus-like nephritis model
Scientific Reports, 2017
Lupus nephritis (LN), one of the most severe outcomes of systemic lupus erythematosus (SLE), is initiated by glomerular deposition of immune-complexes leading to an inflammatory response and kidney failure. Autoantibodies to nuclear antigens and autoreactive B and T cells are central in SLE pathogenesis. Immune mechanisms amplifying this autoantibody production drive flares of the disease. We previously showed that basophils were contributing to LN development in a spontaneous lupus-like mouse model (constitutive Lyn −/− mice) and in SLE subjects through their activation and migration to secondary lymphoid organs (SLOs) where they amplify autoantibody production. In order to study the basophil-specific mechanisms by which these cells contribute to LN development, we needed to validate their involvement in a genetically independent SLE-like mouse model. Pristane, when injected to non-lupus-prone mouse strains, induces a LN-like disease. In this inducible model, basophils were activated and accumulated in SLOs to promote autoantibody production. Basophil depletion by two distinct approaches dampened LN-like disease, demonstrating their contribution to the pristaneinduced LN model. These results enable further studies to decipher molecular mechanisms by which basophils contribute to lupus progression.
Analysis of Peripheral Blood Basophils in Pediatric Systemic Lupus Erythematosus
Diagnostics
Basophils are the least abundant circulating leukocytes, and their immunological role has not yet been completely elucidated. There is evidence supporting their immunomodulatory role in several pathological settings; recently, studies in both experimental models and humans suggested that basophil homeostasis may be altered in systemic lupus erythematosus (SLE). Here, we first assessed circulating basophils in children affected with pediatric SLE (pSLE). In this cross-sectional study, circulating basophils were enumerated by fluorescence-based flow cytometry analysis in children affected with pSLE, in addition to children suffering from juvenile idiopathic arthritis (JIA) or non-inflammatory/non-rheumatic conditions. This study included 52 pediatric patients distributed in these three groups. We observed a statistically significant reduction of peripherally circulating basophils in children with pSLE compared to the other two groups of patients. This preliminary study is consistent w...