Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges

Различия в роли возраста, пола и генетики в формировании транскрипционной вариабельности иммунных ответов человека на микробные воздействия
Barbara Piasecka, Darragh Duffy, Alejandra Urrutia, Hélène Quach, Étienne Patin, Céline Posseme, Jacob Bergstedt, Bruno Charbit, Vincent Rouilly, Cameron Ross MacPherson, Milena Hasan, Benoît Albaud, David Gentien, Jacques Fellay, Matthew L. Albert, Lluís Quintana‐Murci, Laurent Abel, Andrés Alcover, Hugues Aschard, Kalle Åström, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James P. Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Magnus Fontes, António A. Freitas, Odile Gelpi, Ivo Gomperts-Boneca, Serge Herçberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Sandra Pellegrini, Stanislas Pol, Antonio Raussel, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Éric Tartour, Antoine Toubert, Marie‐Noëlle Ungeheuer
2017-12-27
SCID:  54.1/28gahfhz Discuss with AI
genetic variantshuman immune responsesimmune-related diseasesmicrobial challengestranscriptional variation
Abstract (AI)
Significance Identifying the drivers of the interindividual diversity of the human immune system is crucial to understand their consequences on immune-mediated diseases. By examining the transcriptional responses of 1,000 individuals to various microbial challenges, we show that age and sex influence the expression of many immune-related genes, but their effects are overall moderate, whereas genetic factors affect a smaller gene set but with a stronger effect. We identify numerous genetic variants that affect transcriptional variation on infection, many of which are associated with autoimmune or inflammatory disorders. These results enable additional exploration of the role of regulatory variants in the pathogenesis of immune-related diseases and improve our understanding of the respective effects of age, sex, and genetics on immune response variation.
Key Findings
1
Age and sex influence expression of many immune-related genes, but their overall effects are moderate.
2
Analysis of transcriptional responses from 1,000 individuals reveals distinct contributions of age, sex, and genetics to immune-response variation.
3
Genetic factors influence a smaller set of genes but exert stronger effects on transcriptional variation during microbial challenge.
4
Numerous genetic variants affecting infection-induced transcriptional variation are associated with autoimmune or inflammatory disorders.
5
The findings support investigating regulatory variants as contributors to immune-related disease pathogenesis and clarify demographic versus genetic effects on immune responses.
Research Object

Transcriptional responses of 1,000 individuals to various microbial challenges

Research Subject

The effects of age, sex, and genetic variation on interindividual immune-response transcriptional variation, including infection-responsive regulatory variants

Publication Details
Publication Date
2017-12-27
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Authors
Barbara Piasecka
Darragh Duffy
Alejandra Urrutia
Hélène Quach
Étienne Patin
Céline Posseme
Jacob Bergstedt
Bruno Charbit
Vincent Rouilly
Cameron Ross MacPherson
Milena Hasan
Benoît Albaud
David Gentien
Jacques Fellay
Matthew L. Albert
Lluís Quintana‐Murci
Laurent Abel
Andrés Alcover
Hugues Aschard
Kalle Åström
Philippe Bousso
Pierre Bruhns
Ana Cumano
Caroline Demangel
Ludovic Deriano
James P. Di Santo
Françoise Dromer
Gérard Eberl
Jost Enninga
Magnus Fontes
António A. Freitas
Odile Gelpi
Ivo Gomperts-Boneca
Serge Herçberg
Olivier Lantz
Claude Leclerc
Hugo Mouquet
Sandra Pellegrini
Stanislas Pol
Antonio Raussel
Lars Rogge
Anavaj Sakuntabhai
Olivier Schwartz
Benno Schwikowski
Spencer Shorte
Vassili Soumelis
Frédéric Tangy
Éric Tartour
Antoine Toubert
Marie‐Noëlle Ungeheuer
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