Background and Aim: Immune function differs between the sexes but the mechanism for this is not known. Sex steroid receptors have been found to be expressed on various immune cell subtypes, including “non-genomic” membrane bound receptors. The biological function of these molecules and their direct effects on immune function have not been explored. We aimed to determine the biological effects and mode of action of sex steroid receptor signalling on immune cell function.
Methods: Genomic sex steroid signalling involving androgen receptor (AR) and estrogen receptors (ERα and ERβ) in T lymphocytes was assessed using qRT-PCR. Readout genes were known to be sex steroid dependent in other cell types and expressed in T lymphocytes. Effector function of flu-specific T lymphocytes was measured by intracellular staining for interferon gamma following antigen presentation in the context of AR activation or blockade. Non-genomic signalling was screened using a calcium flux assay to indicate activation of unconventional pathways in response to AR activation or blockade.
Results: Up regulation of AR and ER regulated genes in response to dihydrotestosterone and 17β-estradiol respectively was observed in control cell lines where genomic signalling is known to be intact but not in T lymphocytes, providing evidence for a lack of genomic AR and ER signalling in T lymphocytes. Preliminary calcium flux experiments suggest both early and delayed effects of androgen signalling, implying possible activation of non-genomic pathways but these results remain to be confirmed. Results of effector function studies are pending.
Conclusion: These results indicate that the AR signalling pathway in T lymphocytes may be at least in part non-genomic; however these results need further confirmation. Comparable non-genomic studies for ER signalling are ongoing.