Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women.

Morgane Griesbeck; Susanne Ziegler; Sophie Laffont; Nikaïa Smith; Lise Chauveau; Phillip Tomezsko; Armon Sharei; Georgio Kourjian; Filippos Porichis; Meghan Hart; Christine D Palmer; Michael Sirignano; Claudia Beisel; Heike Hildebrandt; Claire Cénac; Alexandra-Chloé Villani; Thomas J Diefenbach; Sylvie Le Gall; Olivier Schwartz; Jean-Philippe Herbeuval; Brigitte Autran; Jean-Charles Guéry; J Judy Chang; Marcus Altfeld

doi:10.4049/jimmunol.1501684

Journal articles

Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women.

Morgane Griesbeck ^{1, 2} Susanne Ziegler ³ Sophie Laffont ⁴ Nikaïa Smith ⁵ Lise Chauveau ⁶ Phillip Tomezsko ² Armon Sharei ⁷ Georgio Kourjian ² Filippos Porichis ² Meghan Hart ² Christine D Palmer ² Michael Sirignano ² Claudia Beisel ^{3, 8} Heike Hildebrandt ³ Claire Cénac ⁴ Alexandra-Chloé Villani ⁹ Thomas J Diefenbach ² Sylvie Le Gall ² Olivier Schwartz ⁶ Jean-Philippe Herbeuval ⁵ Brigitte Autran ¹ Jean-Charles Guéry ⁴ J Judy Chang ^{10, 2} Marcus Altfeld ^{2, 3}

1 CIMI - Centre d'Immunologie et de Maladies Infectieuses

2 Ragon Institute of MGH, MIT and Harvard

3 Heinrich-Pette-Institut

4 CPTP - Centre de Physiopathologie Toulouse Purpan

5 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques

6 Virus et Immunité

7 Koch Institute for Integrative Cancer Research

8 Medical Department [Hamburg]

9 BROAD INSTITUTE - Broad Institute of MIT and Harvard

10 Department of Infectious Diseases [Monash]

Abstract : Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α-secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (Esr1) gene in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression in pDCs and IFN-α production. IRF5 mRNA levels furthermore correlated with ESR1 mRNA levels in human pDCs, consistent with IRF5 regulation at the transcriptional level by ESR1. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation.

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Journal articles

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Life Sciences [q-bio]

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Submitted on : Tuesday, September 27, 2016 - 11:17:25 AM
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Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women.

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