TY - JOUR
T1 - IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus
AU - Geginat, J.
AU - Vasco, M.
AU - Gerosa, M.
AU - Tas, S. W.
AU - Pagani, M.
AU - Grassi, F.
AU - Flavell, R. A.
AU - Meroni, Pl.
AU - Abrignani, S.
PY - 2019
Y1 - 2019
N2 - Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterised by the production of pathogenic autoantibodies against nuclear self-antigens. The anti-inflammatory and tolerogenic cytokine Interleukin-10 appears to play a paradoxical pathogenic role in SLE and is therefore currently therapeutically targeted in clinical trials. It is generally assumed that the pathogenic effect of IL-10 in SLE is due to its growth and differentiation factor activity on autoreactive B-cells, but effects on other cells might also play a role. To date, a unique cellular source of pathogenic IL-10 in SLE has not been identified. In this review, we focus on the contribution of different CD4+T-cell subsets to IL-10 and autoantibody production in SLE. In particular, we discuss that IL-10 produced by different subsets of adaptive regulatory T-cells, follicular helper T-cells and extra-follicular B-helper T-cells is likely to have different effects on autoreactive B-cell responses. A better understanding of the role of IL-10 in B-cell responses and lupus would allow to identify the most promising therapies for individual SLE patients in the future.
AB - Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterised by the production of pathogenic autoantibodies against nuclear self-antigens. The anti-inflammatory and tolerogenic cytokine Interleukin-10 appears to play a paradoxical pathogenic role in SLE and is therefore currently therapeutically targeted in clinical trials. It is generally assumed that the pathogenic effect of IL-10 in SLE is due to its growth and differentiation factor activity on autoreactive B-cells, but effects on other cells might also play a role. To date, a unique cellular source of pathogenic IL-10 in SLE has not been identified. In this review, we focus on the contribution of different CD4+T-cell subsets to IL-10 and autoantibody production in SLE. In particular, we discuss that IL-10 produced by different subsets of adaptive regulatory T-cells, follicular helper T-cells and extra-follicular B-helper T-cells is likely to have different effects on autoreactive B-cell responses. A better understanding of the role of IL-10 in B-cell responses and lupus would allow to identify the most promising therapies for individual SLE patients in the future.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85075193232&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31735515
U2 - https://doi.org/10.1016/j.smim.2019.101330
DO - https://doi.org/10.1016/j.smim.2019.101330
M3 - Review article
C2 - 31735515
SN - 1044-5323
VL - 44
JO - Seminars in Immunology
JF - Seminars in Immunology
M1 - 101330
ER -