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Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus

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Abstract

Biases in the distribution and phenotype of T, B, and antigen-presenting cell populations are strongly connected to mechanisms of disease development in mouse models of systemic lupus erythematosus (SLE). Here, we describe longitudinal changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and spleen from two lupus-prone strains (MRL/lpr and B6.Sle1.Sle2.Sle3 tri-congenic mice), and how they integrate in our present understanding of the pathogenesis of the disease. In particular, we focus on (autoreactive) T cell activation patterns in lupus-prone mice. Break of T cell tolerance to chromatin constituents (histone peptides) is key to the development of the disease and is related to T cell intrinsic defects, contributed by genetic susceptibility factors and by extrinsic amplificatory mechanisms, in particular over-stimulation by antigen-presenting cells. We also describe shifts in B cell sub-populations, going from skewed immature B cell populations as an indication of disturbed central and peripheral tolerance checkpoints, to enriched long-lived plasma cells, which are key to persistent autoantibody production in the disease. B cell activation mechanisms in SLE are both T cell-dependent (break of tolerance and production of specific autoantibodies) and -independent (polyclonal B cell activation, production of autoantibodies by long-lived plasma cells). By providing a comprehensive evaluation of B and T cell surface markers in two major mouse models of SLE and a description of their changes before and after disease onset, this review illustrates how the study of lymphoid cell phenotype delivers key information regarding pathogenic pathways and supplies tools to assess the beneficial effects of novel therapeutic interventions.

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Authors and Affiliations

  1. Pôle de Pathologies Rhumatismales Systémiques et Inflammatoires, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

    Aurélie De Groof & Bernard R. Lauwerys

  2. INSERM U1227, UFR Médecine, Brest, France

    Patrice Hémon, Olivier Mignen, Jacques-Olivier Pers & Yves Renaudineau

  3. Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Edward K. Wakeland

  4. Laboratoire d’Immunologie et Immunothérapie, CHRU Brest, Brest, France

    Yves Renaudineau

  5. Department of Rheumatology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

    Bernard R. Lauwerys

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  1. Aurélie De Groof
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  2. Patrice Hémon
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  3. Olivier Mignen
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  5. Edward K. Wakeland
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Correspondence to Bernard R. Lauwerys.

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Funding

This work was supported by a grant from the Fonds National de la Recherche Scientifique. A. De Groof is supported by the “Chaire UCB/UCL sur les rhumatismes inflammatoires et systémiques”. B. Lauwerys is supported in part by the Fonds National de la Recherche Scientifique (Communauté française de Belgique), and P. Hemon by a SATT Ouest Valorisation grant.

Ethical Approval

All animal experiments reported in this manuscript were approved by the ethical committee of the Université catholique de Louvain (Secteur des Sciences de la Santé), and by the ethical committee of the Université de Bretagne Occidentale (Brest).

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De Groof, A., Hémon, P., Mignen, O. et al. Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus. Clinic Rev Allerg Immunol 53, 181–197 (2017). https://doi.org/10.1007/s12016-017-8605-8

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