Sex differences matter in the gut: effect on mucosal immune activation and inflammation

Sankaran-Walters, Sumathi; Macal, Monica; Grishina, Irina; Nagy, Lauren; Goulart, Larissa; Coolidge, Kathryn; Li, Jay; Fenton, Anne; Williams, Theodore; Miller, Mary K; Flamm, Jason; Prindiville, Thomas; George, Michael; Dandekar, Satya
June 2013
Biology of Sex Differences;2013, Vol. 4 Issue 1, p1
Academic Journal
Background: Women and men have diverse responses to many infectious diseases. These differences are amplified following menopause. However, despite extensive information regarding the effects of sex hormones on immune cells, our knowledge is limited regarding the effects of sex and gender on the function of the mucosal immune system. Sex differences also manifest in the prevalence of gut associated inflammatory and autoimmune disorders, including Crohn's disease, ulcerative colitis and Celiac disease. It is thus hypothesized that a baseline sex-associated difference in immune activation may predispose women to inflammation-associated disease. Methods: Peripheral blood samples and small intestinal biopsies were obtained from 34 healthy men and women. Immunophenotypic analysis of isolated lymphocytes was performed by flow cytometry. Oligonucleotide analysis was used to study the transcriptional profile in the gut mucosal microenvironment while real-time PCR analysis was utilized to identify differential gene expression in isolated CD4+ T cells. Transcriptional analysis was confirmed by protein expression levels for genes of interest using fluorescent immunohistochemistry. Data was analyzed using the GraphPad software package. Results: Women had higher levels of immune activation and inflammation-associated gene expression in gut mucosal samples. CD4+ and CD8+ T cells had a significantly higher level of immune activation-associated phenotype in peripheral blood as well as in gut associated lymphoid tissue along with higher levels of proliferating T cells. CD4+ T cells that showed upregulation of IL1β as well as the TH17 pathway-associated genes contributed a large part of the inflammatory profile. Conclusion: In this study, we demonstrated an upregulation in gene expression related to immune function in the gut microenvironment of women compared to men, in the absence of disease or pathology. Upon closer investigation, CD4+ T cell activation levels were higher in the LPLs in women than in men. Sex differences in the mucosal immune system may predispose women to inflammation-associated diseases that are exacerbated following menopause. Our study highlights the need for more detailed analysis of the effects of sex differences in immune responses at mucosal effector sites.


Related Articles

  • Sterile inflammation - do innate lymphoid cell subsets play a role? Russell, Shane E.; Walsh, Patrick T. // Frontiers in Immunology;Aug2012, Vol. 3, p1 

    The recent identification of several novel innate lymphoid cell (iLC) subsets has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets toward the pathogenesis of human disease remains largely to be determined, it...

  • Rat mesangial cells exhibit sex-specific profibrotic and proinflammatory phenotypes. Pawluczyk, Izabella Z. A.; Tan, Eddie K. C.; Harris, Kevin P. G. // Nephrology Dialysis Transplantation;Jun2009, Vol. 24 Issue 6, p1753 

    Background. Chronic renal disease progresses more rapidly in males compared to females. This study investigated whether there were any inherent differences between male and female mesangial cells that could contribute to this phenomenon and whether these differences could be modulated by sex...

  • Which Gender is Better Positioned in the Process of Liver Surgery? Male or Female? Yukihiro Yokoyama; Masato Nagino; Yuji Nimura // Surgery Today;Oct2007, Vol. 37 Issue 10, p823 

    Abstract  Liver surgery is a process which induces various types of stress on the liver including the total occlusion of the blood inflow, hemorrhage, massive volume reduction, and postoperative infection. Animal studies have shown a gender dimorphic response of the liver for various...

  • Age-Specific Sex-Related Differences in Infections: A Statistical Analysis of National Surveillance Data in Japan. Eshima, Nobuoki; Tokumaru, Osamu; Hara, Shohei; Bacal, Kira; Korematsu, Seigo; Karukaya, Shigeru; Uruma, Kiyo; Okabe, Nobuhiko; Matsuishi, Toyojiro // PLoS ONE;Jul2012, Vol. 7 Issue 7, p1 

    Background: To prevent and control infectious diseases, it is important to understand how sex and age influence morbidity rates, but consistent clear descriptions of differences in the reported incidence of infectious diseases in terms of sex and age are sparse. Methods and Findings: Data from...

  • Immunological Sex Differences in Socially Promiscuous African Ground Squirrels. Manjerovic, Mary Beth; Waterman, Jane M. // PLoS ONE;Jun2012, Vol. 7 Issue 6, p1 

    Differences in how males and females respond to foreign antigens are common across taxa. Such sexual differences in the immune system are predicted to be greater in species with high promiscuity and sociality as these factors increase the likelihood of disease transmission. Intense sperm...

  • Innate Immunity in the Mucosal Immune System. Nochi, Tomonori; Kiyono, Hiroshi // Current Pharmaceutical Design;Nov2006, Vol. 12 Issue 32, p4203 

    The mucosal immune system is equipped with unique innate and acquired defense mechanisms which provide a first line of protection against ingested and inhaled infectious agents. Peyer's patches (PPs) and nasopharynx-associated lymphoid tissue (NALT) have been shown to be important inductive...

  • The Achilles Heel of the Trojan Horse Model of HIV-1 trans-Infection. Cavrois, Marielle; Neidleman, Jason; Greene, Warner C. // PLoS Pathogens;Jun2008, Vol. 4 Issue 6, p1 

    To ensure their survival, microbial pathogens have evolved diverse strategies to subvert host immune defenses. The human retrovirus HIV-1 has been proposed to hijack the natural endocytic function of dendritic cells (DCs) to infect interacting CD4 T cells in a process termed trans-infection....

  • The Sex Differences of Morphology and Immunology of SIRS of Newborn Wistar Rats. Kosyreva, A. M. // ISRN Otolaryngology;2014, p1 

    The sex differences of infection and inflammatory diseases particularly appear at reproductive age and depend on the sex hormone level, varied between male and female. There are a few sets of data about the sex differences of infection and inflammatory diseases course, including systemic...

  • The influence of sex on disease. Bishop, Louis Faugeres; Pace, Brian P. // JAMA: Journal of the American Medical Association;9/16/98, Vol. 280 Issue 11, p962e 

    Reprints an article that appeared in the September 17, 1898 issue of `Journal of the American Medical Association,' which deals with the influence of sex of the course of general disease.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics