(Q29405)
Statements
Infectious, inflammatory and autoimmune conditions present differently in males and females. (English)
© 2024. The Author(s). (English)
2024
SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID<sup>1</sup>, similar to observations in other infections<sup>2</sup>. (English)
© 2024. The Author(s). (English)
2024
Females respond more strongly to vaccines, and adverse reactions are more frequent<sup>3</sup>, like most autoimmune diseases<sup>4</sup>. (English)
© 2024. The Author(s). (English)
2024
Immunological sex differences stem from genetic, hormonal and behavioural factors<sup>5</sup> but their relative importance is only partially understood<sup>6-8</sup>. (English)
© 2024. The Author(s). (English)
2024
In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. (English)
© 2024. The Author(s). (English)
2024
Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. (English)
© 2024. The Author(s). (English)
2024
This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. (English)
© 2024. The Author(s). (English)
2024
Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. (English)
© 2024. The Author(s). (English)
2024
These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals. (English)
© 2024. The Author(s). (English)
2024
Tadepally (English)
Lakshmikanth (English)
T
Camila (English)
Consiglio (English)
C
Fabian (English)
Sardh (English)
F
Rikard (English)
Forlin (English)
R
Jun (English)
Wang (English)
J
Ziyang (English)
Tan (English)
Z
Hugo (English)
Barcenilla (English)
H
Lucie (English)
Rodriguez (English)
L
Jamie (English)
Sugrue (English)
J
Peri (English)
Noori (English)
P
Margarita (English)
Ivanchenko (English)
M
Laura (English)
Piñero Páez (English)
L
Laura (English)
Gonzalez (English)
L
Constantin (English)
Habimana Mugabo (English)
C
Anette (English)
Johnsson (English)
A
Åsa (English)
Hallgren (English)
Å
Christian (English)
Pou (English)
C
Yang (English)
Chen (English)
Y
Jaromír (English)
Mikeš (English)
J
Anna (English)
James (English)
A
Per (English)
Dahlqvist (English)
P
Jeanette (English)
Wahlberg (English)
J
Anders (English)
Hagelin (English)
A
Mats (English)
Holmberg (English)
M
Marie (English)
Degerblad (English)
M
Magnus (English)
Isaksson (English)
M
Darragh (English)
Duffy (English)
D
Nils (English)
Landegren (English)
N
4 October 2024
5 September 2024
and J.M. are cofounders of Cytodelics AB (Stockholm, Sweden), which produces and distributes the whole blood cell stabilizer solutions used in this study. (English)
is an executive board member of Kancera AB, scientific advisor for Pixelgen Technologies AB, Helaina Inc., Scailyte AG, Oxford Immune Algorithmics Ltd, Sention Health AB and the Swedish Olympic Committee. (English)
The other authors declare no competing interests. (English)