Shepherd Rebecca, Cheung Ada S, Pang Ken, Saffery Richard, Novakovic Boris
Epigenetics Group, Infection and Immunity Theme, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia.
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
Front Immunol. 2021 Jan 21;11:604000. doi: 10.3389/fimmu.2020.604000. eCollection 2020.
Sexual dimorphism refers to differences between biological sexes that extend beyond sexual characteristics. In humans, sexual dimorphism in the immune response has been well demonstrated, with females exhibiting lower infection rates than males for a variety of bacterial, viral, and parasitic pathogens. There is also a substantially increased incidence of autoimmune disease in females compared to males. Together, these trends indicate that females have a heightened immune reactogenicity to both self and non-self-molecular patterns. However, the molecular mechanisms driving the sexually dimorphic immune response are not fully understood. The female sex hormones estrogen and progesterone, as well as the male androgens, such as testosterone, elicit direct effects on the function and inflammatory capacity of immune cells. Several studies have identified a sex-specific transcriptome and methylome, independent of the well-described phenomenon of X-chromosome inactivation, suggesting that sexual dimorphism also occurs at the epigenetic level. Moreover, distinct alterations to the transcriptome and epigenetic landscape occur in synchrony with periods of hormonal change, such as puberty, pregnancy, menopause, and exogenous hormone therapy. These changes are also mirrored by changes in immune cell function. This review will outline the evidence for sex hormones and pregnancy-associated hormones as drivers of epigenetic change, and how this may contribute to the sexual dimorphism. Determining the effects of sex hormones on innate immune function is important for understanding sexually dimorphic autoimmune diseases, sex-specific responses to pathogens and vaccines, and how innate immunity is altered during periods of hormonal change (endogenous or exogenous).
性二态性是指生物性别之间超出性特征的差异。在人类中，免疫反应中的性二态性已得到充分证实，对于多种细菌、病毒和寄生虫病原体，女性的感染率低于男性。与男性相比，女性自身免疫性疾病的发病率也显著增加。这些趋势共同表明，女性对自身和非自身分子模式具有更高的免疫反应性。然而，驱动性二态性免疫反应的分子机制尚未完全明确。女性性激素雌激素和孕激素，以及男性雄激素，如睾酮，对免疫细胞的功能和炎症能力有直接影响。多项研究已确定了一种性别特异性转录组和甲基化组，独立于已充分描述的X染色体失活现象，这表明性二态性也发生在表观遗传水平。此外，转录组和表观遗传景观的明显改变与激素变化时期同步发生，如青春期、怀孕、更年期和外源性激素治疗。这些变化也反映在免疫细胞功能的变化上。本综述将概述性激素和妊娠相关激素作为表观遗传变化驱动因素的证据，以及这可能如何导致性二态性。确定性激素对固有免疫功能的影响对于理解性二态性自身免疫性疾病、对病原体和疫苗的性别特异性反应，以及在激素变化（内源性或外源性）期间固有免疫如何改变至关重要。
