Sexual dimorphism in immune response genes as a function of puberty.
BACKGROUND
Autoimmune diseases are more prevalent in females than in males, whereas males have higher mortality associated with infectious diseases. To increase our understanding of this sexual dimorphism in the immune system, we sought to identify and characterize inherent differences in immune response programs in the spleens of male and female mice before, during and after puberty.


RESULTS
After the onset of puberty, female mice showed a higher expression of adaptive immune response genes, while males had a higher expression of innate immune genes. This result suggested a requirement for sex hormones. Using in vivo and in vitro assays in normal and mutant mouse strains, we found that reverse signaling through FasL was directly influenced by estrogen, with downstream consequences of increased CD8+ T cell-derived B cell help (via cytokines) and enhanced immunoglobulin production.


CONCLUSIONS
These results demonstrate that sexual dimorphism in innate and adaptive immune genes is dependent on puberty. This study also revealed that estrogen influences immunoglobulin levels in post-pubertal female mice via the Fas-FasL pathway.
Lamason
Rebecca
R
Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rlamaso1@jhmi.edu
Zhao
Po
P
Rawat
Rashmi
R
Davis
Adrian
A
Hall
John C
JC
Chae
Jae Jin
JJ
Agarwal
Rajeev
R
Cohen
Phillip
P
Rosen
Antony
A
Hoffman
Eric P
EP
Nagaraju
Kanneboyina
K
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D053222:Fas Ligand Protein; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005802:Genes, MHC Class II; D006242:Haptoglobins / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000032:analysis; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000502:physiology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology
D004967:Estrogens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006242:Haptoglobins; D008562:Membrane Glycoproteins; D000685:Serum Amyloid A Protein; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D007371:Interferon-gamma