[HTML][HTML] PD-1hiCXCR5–T peripheral helper cells promote B cell responses in lupus via MAF and IL-21

AV Bocharnikov, J Keegan, VS Wacleche, Y Cao… - JCI insight, 2019 - ncbi.nlm.nih.gov
AV Bocharnikov, J Keegan, VS Wacleche, Y Cao, CY Fonseka, G Wang, ES Muise
JCI insight, 2019ncbi.nlm.nih.gov
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathologic
T cell–B cell interactions and autoantibody production. Defining the T cell populations that
drive B cell responses in SLE may enable design of therapies that specifically target
pathologic cell subsets. Here, we evaluated the phenotypes of CD4+ T cells in the
circulation of 52 SLE patients drawn from multiple cohorts and identified a highly expanded
PD-1 hi CXCR5–CD4+ T cell population. Cytometric, transcriptomic, and functional assays …
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathologic T cell–B cell interactions and autoantibody production. Defining the T cell populations that drive B cell responses in SLE may enable design of therapies that specifically target pathologic cell subsets. Here, we evaluated the phenotypes of CD4+ T cells in the circulation of 52 SLE patients drawn from multiple cohorts and identified a highly expanded PD-1 hi CXCR5–CD4+ T cell population. Cytometric, transcriptomic, and functional assays demonstrated that PD-1 hi CXCR5–CD4+ T cells from SLE patients are T peripheral helper (Tph) cells, a CXCR5–T cell population that stimulates B cell responses via IL-21. The frequency of Tph cells, but not T follicular helper (Tfh) cells, correlated with both clinical disease activity and the frequency of CD11c+ B cells in SLE patients. PD-1 hi CD4+ T cells were found within lupus nephritis kidneys and correlated with B cell numbers in the kidney. Both IL-21 neutralization and CRISPR-mediated deletion of MAF abrogated the ability of Tph cells to induce memory B cell differentiation into plasmablasts in vitro. These findings identify Tph cells as a highly expanded T cell population in SLE and suggest a key role for Tph cells in stimulating pathologic B cell responses.
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