About this Research Topic
Androgens are produced in both males and females, albeit at different levels, and play major roles in a variety of biological processes such as growth, maintenance of secondary sex characteristics at puberty, and reproduction, including spermatogenesis and muscle development. Androgens and their metabolites are also involved in neurogenesis, hematopoiesis, and the regulation of hepatic enzymes and adipocytes. Androgens may act via direct binding by the androgen receptor (AR) or via binding to non-classical ARs, either directly or indirectly. Androgen:AR complexes act as transcription factors promoting gene regulation via binding to androgen response elements (AREs). From an immunological perspective, androgens are known to play key roles in immune cell development and differentiation and in orchestrating immune functions under both normal and pathological conditions. For example, under homeostasis, androgens have been demonstrated to inhibit B cell lymphopoiesis while promoting myelopoisis and erythropoiesis in the bone marrow.
Due to their ability to modulate immune responses, sex hormones are also now being considered as important factors in determining differential susceptibility to infections, in driving autoimmune diseases, and in pre-disposition to cancer in males versus females. For example, many autoimmune disorders display a strong female bias, with up to 90% of patients being females. In the context of infection, males have been reported to often take longer to respond and recover from infections. In some instances, males also appear to be more susceptible to non-reproductive cancers from intestinal organs such as the bladder, the bowel, the liver, the kidney but also from the skin, potentially aligning with the more general suppressive function of androgens on the immune system which might be carried forward in the response to tumors. Such observations have stimulated the establishment of animal-based studies aimed at studying the effects of deregulated male and female sex hormone production in a variety of disease settings. Results from such studies generally support the hypothesis that male sex hormones (androgens) are immunoinhibitory due to their ability to effectively dampen immune reactivity, while female sex hormones (estrogens) are immunostimulatory.
However, the mechanisms by which sex hormones regulate / deregulate the immune system remain poorly understood. AREs have been identified in the regulatory region of a number of immune-associated genes (e.g. pro-inflammatory cytokines, toll-like receptors and co-stimulatory molecules), offering some explanation for the regulatory properties of androgens in the immune system. Furthermore, the binding of androgens to non-classical ARs also modulates transcriptional and non-transcriptional responses, adding further complexity to the impact of androgens on immunity. Further investigation is needed to gain further insight into the effects of sex hormones in different immune populations at the molecular level.
Given that male and female sex hormones differentially regulate immune responses in mouse and man, when treating immune-related pathologies, it seems likely that males and females will respond differently to standard preventative or treatment strategies. One well-known example is the reduced response to vaccination in males which has been observed with a large variety of vaccine candidates including Influenza or Hepatitis B vaccines. However, an adaption of the vaccine dosage has never been considered. On the treatment side, there are more and more studies for sex differences in terms of treatment, survival or mortality rates, such in the psychopharmacological treatment of depression, or in the higher higher excess mortality rate in women in myocardial infarction after adjustment for the use of guideline-indicated treatments. Overall, there is still much knowledge missing since even large controlled treatment studies excluded the one or the other sex, but mostly women.
Therefore, understanding the regulatory effects of androgens on immunity should be a priority since we aim to offer personalized medicine for prevention, diagnosis, and treatment of diseases in the future.
This Research Topic calls for submissions specifically related to the regulatory effects of androgens on both innate and adaptive immunity. It welcomes contributions of any of the following article types: Original Research article, Perspective, Mini Review, Clinical Trial, Protocol, Commentary, Opinion paper and Case Reports, concerning, but not limited to, the following topics:
1. Effects of androgens on immune cell development including lymphocytes, myeloid cells, and ILCs, among others
2. Effects of androgens on regulatory immune cell populations with a particular focus on Tregs, Bregs, myeloid-derived suppressor cells (MDSCs) and other immunesuppressive cell subsets.
3. Effects of androgens on immune memory-type cell populations
4. Effects of androgens on the immune response to infections (e.g. viral, bacterial, and/or parasitic)
5. Effects of androgens on the regulation of immune cells in autoimmune diseases
6. Regulation of the androgen receptor expression and function in immune cells
7. Immune regulation by non-classical androgen receptors
Keywords: androgen, sex difference, infection, autoimmunity
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