Format

Send to

Choose Destination
Immunity. 2015 Jun 16;42(6):1159-70. doi: 10.1016/j.immuni.2015.05.012. Epub 2015 Jun 9.

OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response.

Author information

1
University Bordeaux, CIRID, UMR/CNRS 5164, F-33000 Bordeaux, France; CNRS, CIRID, UMR 5164, F-33000 Bordeaux, France.
2
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
3
University Bordeaux, CIRID, UMR/CNRS 5164, F-33000 Bordeaux, France; CNRS, CIRID, UMR 5164, F-33000 Bordeaux, France; CHU de Bordeaux, F-33076 Bordeaux, France.
4
CNRS, Immunopathology and therapeutic chemistry/Laboratory of excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire;University of Strasbourg, F-67081 Strasbourg, France.
5
CNRS, CIRID, UMR 5164, F-33000 Bordeaux, France.
6
CHU de Bordeaux, F-33076 Bordeaux, France.
7
University Bordeaux, CIRID, UMR/CNRS 5164, F-33000 Bordeaux, France; CHU de Bordeaux, F-33076 Bordeaux, France.
8
CNRS, Immunopathology and therapeutic chemistry/Laboratory of excellence MEDALIS, Institut de Biologie Moléculaire et Cellulaire;University of Strasbourg, F-67081 Strasbourg, France; University of Strasbourg Institute for Advanced Study, F-67081 Strasbourg, France.
9
Dynavax Technologies Corporation, Berkeley, CA 94710, USA.
10
Baylor Institute for Immunology Research, Dallas, TX 75204, USA. Electronic address: hidekiu@baylorhealth.edu.
11
University Bordeaux, CIRID, UMR/CNRS 5164, F-33000 Bordeaux, France; CNRS, CIRID, UMR 5164, F-33000 Bordeaux, France; Baylor Institute for Immunology Research, Dallas, TX 75204, USA; CHU de Bordeaux, F-33076 Bordeaux, France. Electronic address: patrick.blanco@chu-bordeaux.fr.

Abstract

Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.

PMID:
26070486
PMCID:
PMC4570857
DOI:
10.1016/j.immuni.2015.05.012
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center