title: Sex impacts Th1 cells, Tregs, and DCs in both intestinal and systemic immunity in a mouse strain and location-dependent manner.
abstract: BACKGROUND
  Males and females have a different predisposition for the development of intestinal disorders, like inflammatory bowel disease (IBD). We hypothesized that sex specific differences in intestinal immune responses may underlie this bias. To test this hypothesis, we studied sex differences in immune cell populations in the Peyer's patches (PP). For comparison with systemic immunity, we studied spleen cells.
  
  
  METHODS
  Two mouse strains with different susceptibility for developing colitis (BALB/c and C57Bl/6) were used. Using flow cytometry, we measured the percentage of T cells, Th1, Th17, and Treg cells in the PP and spleen. In addition, we measured the percentages of NK cells, macrophages, myeloid, and lymphoid dendritic cells (DCs) and their expression of CD80 and CD103. Moreover, we measured percentages of monocyte subsets in the peripheral circulation. Results were tested using two-way ANOVA, p < 0.05.
  
  
  RESULTS
  Males had a lower percentage of T cells in both PP and spleen (PP BALB/c 22.1 %, B6 13.6 %; spleen BALB/c 4.7 %, B6 19.9 %) but a higher percentage of Th1 cell in both tissues (PP BALB/c 350 %, B6 109.5 %; spleen BALB/c 48.7 %, B6 41.9 %) than females. They also had a higher percentage of Tregs in the spleen than females (BALB/c 20.5 %, B6 4.5 %). Furthermore, males had a higher percentage of CD80(+) DCs in both the PP and spleen (lymphoid DCs in PP BALB/c 104.7 %, B6 29.6 %; spleen BALB/c 72.2 %, B6 44.2 %; myeloid DCs in PP BALB/c 80.5 %, B6 93.3 %; spleen BALB/c 88.5 %, B6 50.8 %) and a higher percentage of lymphoid CD103(+) DCs in the spleen than females (BALB/c 41.5 %, B6 28.3 %). The percentage of NK cells was decreased in the spleen (BALB/c 12.5 %, B6 25.1 %) but increased in the PP (BALB/c 75.7 %, B6 78.6 %) of males as compared with females. Strain differences were also found in the PP; BALB/c mice had a higher percentage of T cells (males 58.1 %, females 75.5 %), a higher Th/Tc ratio (males 81.0 %, females 134.2 %), less FoxP3(+)CD25(-) T cells (males 14.6 %, females 30.0 %), more DCs (males 14.8 %, females 15.7 %) and macrophages (males 67.9 %, females 141.2 %), and more NK cells (males 160 %, females164.3 %) than BALB/c mice.
  
  
  CONCLUSIONS
  In this study, we show sex differences in intestinal and peripheral immune populations. These differences may underlie sex differences in intestinal disorders like IBD, and this information may be an important knowledge for the treatment of intestinal-related diseases.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands ; Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Marlies
authors.initials: M
authors.lastname: Elderman
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands ; Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: van Beek
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands ; Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Eelke
authors.initials: E
authors.lastname: Brandsma
authors.affiliation: Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: de Haan
authors.affiliation: Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Huub
authors.initials: H
authors.lastname: Savelkoul
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands ; Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
authors.affiliation: Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen, The Netherlands ; Department of Obstetrics and Gynaecology, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Faas
keywords: BALB/c; C57Bl/6; Dendritic cells; Intestinal immune cells; Macrophages; Natural killer cells; Peyer’s patches; Sex differences; T cells