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

Clément Jacquemin; Nathalie Schmitt; Cécile Contin-Bordes; Yang Liu; Priya Narayanan; Julien Seneschal; Typhanie Maurouard; David Dougall; Emily Spence Davizon; Hélène Dumortier; Isabelle Douchet; Loïc Raffray; Christophe Richez; Estibaliz Lazaro; Pierre Duffau; Marie Elise Truchetet; Liliane Khoryati; Patrick Mercié; Lionel Couzi; Pierre Merville; Thierry Schaeverbeke; Jean François Viallard; Jean Luc Pellegrin; Jean François Moreau; Sylviane Muller; Sandy Zurawski; Robert L. Coffman; Virginia Pascual; Hideki Ueno; Patrick Blanco

doi:10.1016/j.immuni.2015.05.012

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

Clément Jacquemin, Nathalie Schmitt, Cécile Contin-Bordes, Yang Liu, Priya Narayanan, Julien Seneschal, Typhanie Maurouard, David Dougall, Emily Spence Davizon, Hélène Dumortier, Isabelle Douchet, Loïc Raffray, Christophe Richez, Estibaliz Lazaro, Pierre Duffau, Marie Elise Truchetet, Liliane Khoryati, Patrick Mercié, Lionel Couzi, Pierre MervilleThierry Schaeverbeke, Jean François Viallard, Jean Luc Pellegrin, Jean François Moreau, Sylviane Muller, Sandy Zurawski, Robert L. Coffman, Virginia Pascual, Hideki Ueno, Patrick Blanco

Research output: Contribution to journal › Article › peer-review

178 Scopus citations

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⁺ Tcells 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.

Original language	English
Pages (from-to)	1159-1170
Number of pages	12
Journal	Immunity
Volume	42
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2015.05.012
State	Published - 16 Jun 2015
Externally published	Yes

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Jacquemin, C., Schmitt, N., Contin-Bordes, C., Liu, Y., Narayanan, P., Seneschal, J., Maurouard, T., Dougall, D., Davizon, E. S., Dumortier, H., Douchet, I., Raffray, L., Richez, C., Lazaro, E., Duffau, P., Truchetet, M. E., Khoryati, L., Mercié, P., Couzi, L., ... Blanco, P. (2015). OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response. Immunity, 42(6), 1159-1170. https://doi.org/10.1016/j.immuni.2015.05.012

@article{001d3f7b51bc4ceeaaa215295226040b,

title = "OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response",

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+ Tcells 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.",

author = "Cl{\'e}ment Jacquemin and Nathalie Schmitt and C{\'e}cile Contin-Bordes and Yang Liu and Priya Narayanan and Julien Seneschal and Typhanie Maurouard and David Dougall and Davizon, {Emily Spence} and H{\'e}l{\`e}ne Dumortier and Isabelle Douchet and Lo{\"i}c Raffray and Christophe Richez and Estibaliz Lazaro and Pierre Duffau and Truchetet, {Marie Elise} and Liliane Khoryati and Patrick Merci{\'e} and Lionel Couzi and Pierre Merville and Thierry Schaeverbeke and Viallard, {Jean Fran{\c c}ois} and Pellegrin, {Jean Luc} and Moreau, {Jean Fran{\c c}ois} and Sylviane Muller and Sandy Zurawski and Coffman, {Robert L.} and Virginia Pascual and Hideki Ueno and Patrick Blanco",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = jun,

day = "16",

doi = "10.1016/j.immuni.2015.05.012",

language = "English",

volume = "42",

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journal = "Immunity",

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Jacquemin, C, Schmitt, N, Contin-Bordes, C, Liu, Y, Narayanan, P, Seneschal, J, Maurouard, T, Dougall, D, Davizon, ES, Dumortier, H, Douchet, I, Raffray, L, Richez, C, Lazaro, E, Duffau, P, Truchetet, ME, Khoryati, L, Mercié, P, Couzi, L, Merville, P, Schaeverbeke, T, Viallard, JF, Pellegrin, JL, Moreau, JF, Muller, S, Zurawski, S, Coffman, RL, Pascual, V, Ueno, H & Blanco, P 2015, 'OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response', Immunity, vol. 42, no. 6, pp. 1159-1170. https://doi.org/10.1016/j.immuni.2015.05.012

TY - JOUR

T1 - OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response

AU - Jacquemin, Clément

AU - Schmitt, Nathalie

AU - Contin-Bordes, Cécile

AU - Liu, Yang

AU - Narayanan, Priya

AU - Seneschal, Julien

AU - Maurouard, Typhanie

AU - Dougall, David

AU - Davizon, Emily Spence

AU - Dumortier, Hélène

AU - Douchet, Isabelle

AU - Raffray, Loïc

AU - Richez, Christophe

AU - Lazaro, Estibaliz

AU - Duffau, Pierre

AU - Truchetet, Marie Elise

AU - Khoryati, Liliane

AU - Mercié, Patrick

AU - Couzi, Lionel

AU - Merville, Pierre

AU - Schaeverbeke, Thierry

AU - Viallard, Jean François

AU - Pellegrin, Jean Luc

AU - Moreau, Jean François

AU - Muller, Sylviane

AU - Zurawski, Sandy

AU - Coffman, Robert L.

AU - Pascual, Virginia

AU - Ueno, Hideki

AU - Blanco, Patrick

PY - 2015/6/16

Y1 - 2015/6/16

N2 - 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+ Tcells 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.

AB - 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+ Tcells 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.

UR - http://www.scopus.com/inward/record.url?scp=84937641822&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2015.05.012

DO - 10.1016/j.immuni.2015.05.012

M3 - Article

C2 - 26070486

AN - SCOPUS:84937641822

SN - 1074-7613

VL - 42

SP - 1159

EP - 1170

JO - Immunity

JF - Immunity

IS - 6

ER -

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

Abstract

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