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JCI Insight. 2018 Dec 20;3(24). pii: 122167. doi: 10.1172/jci.insight.122167.

OX40L/OX40 axis impairs follicular and natural Treg function in human SLE.

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INSERM U1035, Immuno-Dermatology, Bordeaux University, Bordeaux, France.
CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France.
Centre hospitalier universitaire de Bordeaux, Bordeaux, France.
Baylor Institute for Immunology Research, Dallas, Texas, USA.


Tregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell-dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3+ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy.


Autoimmune diseases; Autoimmunity; Cellular immune response; Immunology; Lupus

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