2. Academic Validation
  3. OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response

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

  • Immunity. 2015 Jun 16;42(6):1159-70. doi: 10.1016/j.immuni.2015.05.012.
Clément Jacquemin 1,  Nathalie Schmitt 2,  Cécile Contin-Bordes 3,  Yang Liu 2,  Priya Narayanan 2,  Julien Seneschal 3,  Typhanie Maurouard 2,  David Dougall 2,  Emily Spence Davizon 2,  Hélène Dumortier 4,  Isabelle Douchet 5,  Loïc Raffray 6,  Christophe Richez 3,  Estibaliz Lazaro 3,  Pierre Duffau 3,  Marie-Elise Truchetet 3,  Liliane Khoryati 1,  Patrick Mercié 7,  Lionel Couzi 7,  Pierre Merville 3,  Thierry Schaeverbeke 7,  Jean-François Viallard 7,  Jean-Luc Pellegrin 7,  Jean-François Moreau 3,  Sylviane Muller 8,  Sandy Zurawski 2,  Robert L Coffman 9,  Virginia Pascual 2,  Hideki Ueno 10,  Patrick Blanco 11
Affiliations

Affiliations

  • 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: [email protected].
  • 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: [email protected].
PMID: 26070486 DOI: 10.1016/j.immuni.2015.05.012
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.

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