Home Medizin Das Immunsystem von Frauen verdrängt Männer, allerdings auf Kosten eines höheren Autoimmunrisikos

Das Immunsystem von Frauen verdrängt Männer, allerdings auf Kosten eines höheren Autoimmunrisikos

von NFI Redaktion

In a review article recently published in the journal Nature Reviews Immunology, researchers summarize the current knowledge on the effects of having two X chromosomes on the composition and function of the immune system.

Scientists have observed that in all age groups, including infants and even before birth, female individuals can overcome infection more quickly than males and show lower mortality post-infection. They also exhibit a stronger response to vaccination, as seen in female mice whose immune response lasted longer and was more resistant to viral and bacterial infections.


Rückblick: Der Zusammenhang zwischen Sex und Immunreaktionen.


Rezension: Der Zusammenhang zwischen Sex und Immunreaktionen. Bildnachweis: Ustyna Shevchuk / Shutterstock

However, these advantages also come with an increased risk for the development of autoimmune diseases such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Sjögren’s syndrome. 80% of autoimmune disease cases are in women, and this proportion has increased over time. These differences may be due to fluctuations in sex hormone levels, gonadal sex hormones, as well as X and Y chromosomes.

Composition of immune cells shows gender-specific differences

Scientists used flow cytometric immunotyping to observe gender-specific differences in humoral, cellular, and innate immune responses, including an increase in (CD)4+ T cells in women, indicating higher thymus function.

Women also have more plasma cells, regulatory T (Treg) cells, CD19+ B cells, mucosal-associated invariant T cells, and naive CD8+ T cells than men. However, men tend to have more CD16+ and CD14+ monocytes, natural killer (NK) cells, and myeloid cells. Gender differences in humoral immunity include high production of IgM antibodies in women.

Mouse strains were also used to identify other gender-specific differences, including higher T and B cells in peripheral blood in women and more NK cells in the spleen in men. However, sexual hormones are not associated with effector function or the number of NK cells.

Sexual hormones influence immune cells

Gene expression in subsets of immune cells differs between men and women, which can be influenced by sexual hormones. Approximately 1.875 transcripts, most of which are autosomal, show gender-specific differences, mainly in one type of immune cell.

Depending on which immune cell or hormone concentration is studied, for instance, estrogens may have anti-inflammatory or pro-inflammatory functions. They also increase the expression of endosomal Toll-like receptors 9 (TLR9), TLR7, and TLR3.

Also, in terms of microbial infections, immune functions can differ between genders. Researchers have found that peritoneal macrophages in female rats express higher levels of TLRs and show enhanced phagocytosis and bacterial elimination. Studies in mouse models of sepsis also showed that males became more frequently ill, and more viable bacteria were recovered from them than from female mice.

Males may also be more prone to endotoxic shock than females, possibly due to their neutrophils having higher TLR3 expression, leading to a stronger production of pro-inflammatory cytokines. However, it is believed that androgens play an anti-inflammatory role, and the mechanisms increasing TLR4 expression in human neutrophils are not well understood.

Reactivation of the X chromosome and female autoimmune disease

During development in female mammals, one X chromosome remains inactive or transcriptionally silenced. This may decrease or even eliminate the enrichment of heterochromatic modifications, leading to myeloproliferative neoplasia, increased polyp formation, or the absence of perceived phenotypes in mouse models. However, these studies suggest that inflammatory stress can reactivate the inactive X chromosome.

Lymphocyte precursor cells and other immune cells lack epigenetic features on the inactive X, which could cause pro-inflammatory genes to be expressed more strongly in response to infections, which is beneficial to women. However, this would also explain why women are more susceptible to autoimmune diseases.

Differences in response to pathogens and vaccinations

Among the observed gender-specific differences in infection rates with pathogens include higher susceptibility to many fungal, bacterial, viral, and parasitic infections in men, and parasitic worm infections in women. Ebola, the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), and human immunodeficiency viruses (HIV) have shown gender-specific differences in replication, coinfection, and transmission rates. Researchers believe this could be explained by the stronger inflammatory responses observed in women.

After vaccination, women often show a stronger antibody response but are also more prone to side effects. They exhibit stronger inflammation near the injection site. Some researchers have suggested re-evaluating vaccine doses for women to reduce the risk of side effects. However, little is known about which X-chromosomal genes could cause these differences.

Conclusions

Overall, the research suggests that biological gender significantly correlates with health and immune system responses. Further studies are needed to understand the molecular and cellular basis for these observed differences between men and women. Such insights are key to developing effective gender-specific treatments for better outcomes.

Journal reference:

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