| Title | OX40L/OX40 axis impairs follicular and natural Treg function in human SLE. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Jacquemin C, Augusto J-F, Scherlinger M, Gensous N, Forcade E, Douchet I, Levionnois E, Richez C, Lazaro E, Duffau P, Truchetet M-E, Seneschal J, Couzi L, Pellegrin J-L, Viallard J-F, Schaeverbeke T, Pascual V, Contin-Bordes C, Blanco P |
| Journal | JCI Insight |
| Volume | 3 |
| Issue | 24 |
| Date Published | 2018 12 20 |
| ISSN | 2379-3708 |
| Keywords | Antigen-Presenting Cells, Autoimmune Diseases, Cell Proliferation, Cytokines, Dendritic Cells, Down-Regulation, Female, Forkhead Transcription Factors, Humans, Immunity, Cellular, Lupus Erythematosus, Systemic, Lymphocyte Activation, Male, Myeloid Cells, OX40 Ligand, Receptors, OX40, T-Lymphocytes, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory |
| Abstract | 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. |
| DOI | 10.1172/jci.insight.122167 |
| Custom 1 | |
| Alternate Journal | JCI Insight |
| PubMed ID | 30568041 |
| PubMed Central ID | PMC6338386 |
| Grant List | U19 AI057234 / AI / NIAID NIH HHS / United States U19 AI082715 / AI / NIAID NIH HHS / United States U19 AI089987 / AI / NIAID NIH HHS / United States |