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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

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, etc.

Immunity. 2015 Jun 16;42(6):1159-70.

PMID: 26070486

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413750	OX40 Ligand human			Price

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