TY - JOUR
T1 - Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus
AU - de Groof, Aurélie
AU - Hémon, Patrice
AU - Mignen, Olivier
AU - Pers, Jacques Olivier
AU - Wakeland, Edward K.
AU - Renaudineau, Yves
AU - Lauwerys, Bernard R.
N1 - Funding Information:
The authors declare that they have no conflict of interest. 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 syst?miques?. B. Lauwerys is supported in part by the Fonds National de la Recherche Scientifique (Communaut? fran?aise de Belgique), and P. Hemon by a SATT Ouest Valorisation grant.
Funding Information:
Funding This work was supported by a grant from the Fonds National de la Recherche Scientifique. A. De Groof is supported by the BChaire 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.
Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - B cell
KW - Flow cytometry
KW - Mouse models
KW - Systemic lupus erythematosus
KW - T cell
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U2 - 10.1007/s12016-017-8605-8
DO - 10.1007/s12016-017-8605-8
M3 - Review article
C2 - 28500565
AN - SCOPUS:85019196397
SN - 1080-0549
VL - 53
SP - 181
EP - 197
JO - Clinical Reviews in Allergy and Immunology
JF - Clinical Reviews in Allergy and Immunology
IS - 2
ER -