Abstract
The last three decades have seen a growing interest in research in the field of immunometabolism, likely because of promising discoveries made in this field. This includes demonstration of the crucial roles of cellular metabolism in the regulation of functional plasticity of various immune cells, their cross talk with major metabolic tissues (and consequently in the regulation of metabolic homeostasis) at the systemic level, and their potential in improving the efficacy of current immunotherapy or developing new therapeutics for a variety of metabolic and immune diseases (Lee YS, Wollam J, Olefsky JM, Cell 172:22–40, 2018). Surprisingly, sex differences, which are integral to metabolic and immune health and disease, have received a short shrift from researchers in this field. The purpose of this chapter in this protocols book in the Immunometabolism: Methods in Molecular Biology series is to bring attention to this understudied, but crucial, feature of immunometabolism within the scientific community. Sex differences in adipose (and by extension, metabolic) and immune functions are pervasive in metabolic and immune health and disease; it is likely that a better insight into them may open new research directions to better capitalize on the promising discoveries made in this field, and thereby contribute to the development of sex-based precision medicine. It is counterintuitive to ignore a fundamental aspect of immunometabolism, and thereby limit our ability to capitalize on its promising features in improving or maintaining health, and for the therapeutic targeting of associated diseases. Here we briefly discuss the potential drivers and touch upon some unanswered questions in sex differences in immunometabolism, especially those that require attention from the scientific community.
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References
Lee YS, Wollam J, Olefsky JM (2018) An integrated view of immunometabolism. Cell 172:22–40
Mishra S, Nyomba BG (2017 Jun) Prohibitin—at the crossroads of obesity-linked diabetes and cancer. Exp Biol Med (Maywood) 242(11):1170–1177
Mishra S, Nyomba BG (2019 Feb) Prohibitin: a hypothetical target for sex-based new therapeutics for metabolic and immune diseases. Exp Biol Med (Maywood) 244(2):157–170
Mauvais-Jarvis F (2015) Sex differences in metabolic homeostasis, diabetes, and obesity. Biol Sex Differ 6:14
Markle JG, Fish EN (2014) SeXX matters in immunity. Trends Immunol 35:97–104
Nair RR, Verma P, Singh K (2017) Immune-endocrine crosstalk during pregnancy. Gen Comp Endocrinol 242:18–23
Lin JH, Zhang SM, Rexrode KM et al (2013) Association between hormones and colorectal cancer risk in men and women. Clin Gastroenterol Hepatol 11:419–424
Butterworth M et al (1967) Influence of sex in immunoglobulin levels. Nature 214:1224–1225
Xu YXZ, Ande SR, Mishra S (2018) Gonadectomy in Mito-Ob mice revealed a sex-dimorphic relationship between prohibitin and sex steroids in adipose tissue biology and glucose homeostasis. Biol Sex Differ 9(1):37
Fischer J, Jung N, Robinson N et al (2015) Sex differences in immune responses to infectious diseases. Infection 43:399–403
González-Arenas A, Neri-Gómez T, Guerra-Araiza C, Camacho-Arroyo I (2004) Sexual dimorphism in the content of progesterone and estrogen receptors, and their cofactors in the lung of adult rats. Steroids 69(5):351–356
Liu S, Sun Q (2018) Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes. J Diabetes 10(6):428–441
Cao J, Yu L, Zhao J, Ma H (2019) Effect of dehydroepiandrosterone on the immune function of mice in vivo and in vitro. Mol Immunol 112:283–290
Balaton BP, Cotton AM, Brown CJ (2015) Derivation of consensus inactivation status for X-linked genes from genome-wide studies. Biol Sex Differ 6:35
Weinberg SE, Sena LA, Chandel NS (2015) Mitochondria in the regulation of innate and adaptive immunity. Immunity 42(3):406–417
Matarrese P, Tieri P, Anticoli S, Ascione B, Conte M, Franceschi C, Malorni W, Salvioli S, Ruggieri A (2019) X-chromosome-linked miR548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis. Cell Death Dis 10(9):673
Xu YXZ, Ande SR, Mishra S (2018) Prohibitin: a new player in immunometabolism. Cancer Lett 415:208–216
Ande SR, Nguyen KH, Nyomba BLG, Mishra S (2016) Prohibitin in adipose and immune functions. Trends Endocrinol Metab 27(8):531–541
Topalian SL, Taube JM, Anders RA, Pardoll DM (2016 May) Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 16(5):275–287
Li Z et al (2012) Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer. Cell 148:72–83
Bojkowska K et al (2012) Liver-specific ablation of Krüppel-associated box-associated protein 1 in mice leads to male-predominant hepatosteatosis and development of liver adenoma. Hepatology 56:1279–1290
Ande SR, Nguyen KH, Grégoire Nyomba BL, Mishra S (2016) Prohibitin-induced, obesity-associated insulin resistance and accompanying low-grade inflammation causes NASH and HCC. Sci Rep 6:23608
Corbit KC, Wilson CG, Lowe D, Tran JL, Vera NB, Clasquin M, Mattis AN, Weiss EJ (2019) Adipocyte JAK2 mediates spontaneous metabolic liver disease and hepatocellular carcinoma. JCI Insight 5. pii: 131310
Xu H, Cao D, He A, Ge W (2019) The prognostic role of obesity is independent of sex in cancer patients treated with immune checkpoint inhibitors: a pooled analysis of 4090 cancer patients. Int Immunopharmacol 74:105745
Cortellini A, Bersanelli M, Buti S et al (2019) A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable. J Immunother Cancer 7(1):57
Acknowledgments
Research in the laboratory of SM is supported by Natural Sciences and Engineering Research Council of Canada (RGPIN-2017-04962), Research Manitoba, Health Sciences Centre Foundation, and URGP-University of Manitoba.
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Mishra, S., Bassi, G., Xu, Y.X.Z. (2020). Sex Differences in Immunometabolism: An Unexplored Area. In: Mishra, S. (eds) Immunometabolism. Methods in Molecular Biology, vol 2184. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0802-9_18
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DOI: https://doi.org/10.1007/978-1-0716-0802-9_18
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