Evidence map›Paper›PMID 30276444›Full record

ReviewSeminars in immunopathology2019

Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape from X chromosome inactivation.

Mélanie Souyris, José E Mejía, Julie Chaumeil, Jean-Charles Guéry

Abstract readReview
PubMed Publisher
In one paragraph

Review in Seminars in immunopathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

116 citing papers in PubMed, 1 synthesis or guideline pooled it, 199 citations in OpenAlex.

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  18. Sex Bias in Autoimmunity: New Findings and New Opportunities.JID innovations : skin science from molecules to population health · 2025
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56 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Mélanie SouyrisCentre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, INSERM, CNRS, Université Paul Sabatier, 31300, Toulouse, France.
José E MejíaCentre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, INSERM, CNRS, Université Paul Sabatier, 31300, Toulouse, France.
Julie ChaumeilInstitut Cochin, INSERM U1016, CNRS UMR8104, Université Paris-Descartes, 75014, Paris, France.
Jean-Charles GuéryCentre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, INSERM, CNRS, Université Paul Sabatier, 31300, Toulouse, France. Jean-Charles.Guery@inserm.fr.ORCID 0000-0003-4499-3270
Centre National de la Recherche Scientifique · FR

Funding

ALTERNATIVE PATHWAYS OF T CELL ACTIVATIONK08AR002017 · NIAMS · VANDERBILT UNIVERSITY · PI BYRD, VICTOR M · 1998 to 2002
$348k
6 · The paper itself

Abstract

Women develop stronger immune responses than men, with positive effects on the resistance to viral or bacterial infections but magnifying also the susceptibility to autoimmune diseases like systemic lupus erythematosus (SLE). In SLE, the dosage of the endosomal Toll-like receptor 7 (TLR7) is crucial. Murine models have shown that TLR7 overexpression suffices to induce spontaneous lupus-like disease. Conversely, suppressing TLR7 in lupus-prone mice abolishes SLE development. TLR7 is encoded by a gene on the X chromosome gene, denoted TLR7 in humans and Tlr7 in the mouse, and expressed in plasmacytoid dendritic cells (pDC), monocytes/macrophages, and B cells. The receptor recognizes single-stranded RNA, and its engagement promotes B cell maturation and the production of pro-inflammatory cytokines and antibodies. In female mammals, each cell randomly inactivates one of its two X chromosomes to equalize gene dosage with XY males. However, 15 to 23% of X-linked human genes escape X chromosome inactivation so that both alleles can be expressed simultaneously. It has been hypothesized that biallelic expression of X-linked genes could occur in female immune cells, hence fostering harmful autoreactive and inflammatory responses. We review here the current knowledge of the role of TLR7 in SLE, and recent evidence demonstrating that TLR7 escapes from X chromosome inactivation in pDCs, monocytes, and B lymphocytes from women and Klinefelter syndrome men. Female B cells where TLR7 is thus biallelically expressed display higher TLR7-driven functional responses, connecting the presence of two X chromosomes with the enhanced immunity of women and their increased susceptibility to TLR7-dependent autoimmune syndromes.

Indexed as

Chromosomes, Human, XGenetic Predisposition to DiseaseLupus Erythematosus, SystemicSex CharacteristicsToll-Like Receptor 7AnimalsFemaleGene DosageHumansMaleMembrane GlycoproteinsMiceX Chromosome InactivationMembrane GlycoproteinsTLR7 protein, humanTlr7 protein, mouseToll-Like Receptor 7Sexual dimorphismSystemic lupus erythematosusToll-like receptor 7X chromosome dosageX chromosome inactivation escape

Identifiers

PMID30276444
OpenAlexW2894783114

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.