Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy.

Females exhibit more favorable outcomes for certain infections but a higher incidence of autoimmune disease compared to males.

• Sex differences in immune system development and response to pathogens have been well documented.
• These sex differences are at least partially mediated by sex hormones signaling through sex hormone receptors.
• The paper frames this as an established finding that motivates investigation into hormonal and epigenetic mechanisms.

Sex hormone receptors remodel chromatin structure and epigenetic marks in different cellular contexts in humans.

• The paper summarizes current knowledge of how sex hormone receptors remodel the regulatory chromatin landscape of cells.
• Chromatin remodeling by sex hormone receptors is described as occurring in different contexts in humans.
• The epigenome is described as 'fundamental to specifying cell identity and function' and as reflecting past exposures.

Epigenetic variation can influence cellular responses to future stimuli, with implications for susceptibility to infection and complex inflammatory disease.

• Because the epigenome reflects past exposures, epigenetic variation is described as capable of influencing cellular responses to future stimuli.
• This mechanism has implications for susceptibility to infection and complex inflammatory disease.
• These implications are noted across a range of hormone therapy settings.

Profiling of epigenetic marks in the context of gender-affirming hormone therapy in transgender people is identified as an important and unexplored field of research.

• Gender-affirming hormone therapy is identified as one of the hormone therapy settings with implications for infection susceptibility and inflammatory disease.
• The paper explicitly states that 'profiling of epigenetic marks in the context of gender-affirming hormone therapy is an important unexplored field of research.'
• The review frames this gap in knowledge as a key motivation for the paper.