Sex bias in lymphocytes: Implications for autoimmune diseases

Abstract

Autoimmune diseases are characterized by a significant sex dimorphism, with women showing increased susceptibility to disease. This is, at least in part, due to sex-dependent differences in the immune system that are influenced by the complex interplay between sex hormones and sex chromosomes, with contribution from sociological factors, diet and gut microbiota. Sex differences are evident in the number and function of lymphocyte populations. Women mount a stronger pro-inflammatory response than males, with increased lymphocyte proliferation, activation and pro-inflammatory cytokine production, whereas men display expanded regulatory cell subsets. Ageing alters the immune landscape of men and women in differing ways, resulting in changes in autoimmune disease susceptibility. Here we review the current literature on sex differences in lymphocyte function, the factors that influence this, and the implications for autoimmune disease. We propose that improved understanding of sex bias in lymphocyte function can provide sex-specific tailoring of treatment strategies for better management of autoimmune diseases.

Thymus antibody-secreting cells possess an interferon gene signature and are preferentially expanded in young female mice

“…If this hypothesis is true, the sex bias in early life THY ASC numbers may contribute to the phenotypic and functional differences observed in T cells from females and males. 95 …”

Thymus antibody-secreting cells: once forgotten but not lost

“…In this context, TLR7 in the THY compartment was equivalently expressed between both sexes. As such, the regulatory model we propose may explain why some autoimmune diseases show a loss of sex bias with aging ( 102 ). The THY has been proposed to play a key role in age-associated autoimmunity; however, this has mainly been attributed to disrupted T cell selection and production of regulatory T cells ( 114 , 115 ).…”

Immuno-Stimulating Activity of 1,25-Dihydroxyvitamin D in Blood Cells from Five Healthy People and in Blasts from Five Patients with Leukemias and Pre-Leukemic States

“…The other genes upregulated by 1,25D in all individuals were the ones encoding cathelicidin antimicrobial peptide (CAMP), vitelline membrane outer layer 1 homolog (VMO1), PDZ and LIM domain 4 (PDLIM4), ceruloplasmin (CP) and parvalbumin (PVALB). The data presented in Table 2 indicate that the weakest upregulation was about 2 times in case of VMO1 and PDLIM4, while the strongest upregulation was about 2 18 (~260 000) times in case of CYP24A1 and CP. The list of the genes that were upregulated in all healthy volunteers, and the list of the genes that were upregulated in all patients are presented in the supplementary Table S2a,b.…”

“…The primary goal in the treatment of leukemias is an elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy removes not only proliferating blasts but also prevents the remaining immune cells from being activated, since immune activation is always accompanied by proliferation [ 18 ]. In this way, chemotherapy-induced immunodeficiency adds to the leukemia-induced immunodeficiency.…”