Basophils, IgE, and Autoantibody-Mediated Kidney Disease (original) (raw)
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Basophils and Systemic Lupus Erythematosus in Murine Models and Human Patients
Biology
Basophils are the rarest cell population in the blood. Even though basophils are known to participate in some allergic reactions and immune responses to parasitic infections, their immunological role is still largely elusive. Recent evidence has suggested that in some murine models of systemic lupus erythematosus and lupus-like nephritis, basophils may also be implicated in autoimmunity processes by promoting autoantibody production and tissue injury. We conducted a systematic search to collect the available evidence on basophils’ potential immunomodulatory role in autoimmunity and, particularly, systemic lupus erythematosus. We identified several articles investigating basophils’ role in murine models of lupus (n = 3) and in patients affected with systemic lupus erythematosus (n = 8). Even though the alteration of the “adaptive” immune response is considered the main immunopathological event in systemic lupus erythematosus, the contribution from the mechanisms of “innate” immunity ...
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.
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 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.
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).
Mutual Interaction of Basophils and T Cells in Chronic Inflammatory Diseases
Frontiers in Immunology, 2015
Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high-affinity receptor for IgE (FcεR1), release histamine, inflammatory mediators, and cytokines following FcεR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid, and non-lymphoid tissues, and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcεR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naïve T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2, and Th17 cells, as well as their potential role in IgE-independent non-allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases.
ABSTRACTSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies raised against nuclear antigens and whose production is promoted by autoreactive T follicular helper (TFH) cells. Basophils, by accumulating in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms to be defined. Here, we demonstrate that a functional relationship between TFH cells and basophils occurs in SLO during lupus pathogenesis. On SLE patient blood basophils, PD-L1 expression was upregulated and associated with TFH and TFH2 cell expansions and with disease activity. In two distinct lupus-like mouse models, TFH cell pathogenic accumulation, maintenance and function, and disease activity were dependent on basophils and their expressions of PD-L1 and IL-4. Our study establishes a direct link between basophils and TFH cells in the SLE context that promotes autoreactive IgG production and lupus nephritis pathogenesis. Altering t...