Controlled hypobaric hypoxia increases immunological tolerance by modifying HLA-G expression, a potential therapy to inflammatory diseases

Marina Ziliotto; Raul Marques Rodrigues; José Artur Bogo Chies

doi:10.1016/j.mehy.2020.109664

Controlled hypobaric hypoxia increases immunological tolerance by modifying HLA-G expression, a potential therapy to inflammatory diseases

Med Hypotheses. 2020 Mar 4:140:109664. doi: 10.1016/j.mehy.2020.109664. Online ahead of print.

Authors

Marina Ziliotto¹, Raul Marques Rodrigues¹, José Artur Bogo Chies²

Affiliations

¹ Laboratory of Immunobiology and Immunogenetics, Department of Genetics, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.
² Laboratory of Immunobiology and Immunogenetics, Department of Genetics, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: jabchies@terra.com.br.

PMID: 32155542
DOI: 10.1016/j.mehy.2020.109664

Abstract

One of the most striking characteristics of human beings is the incredible capacity to adapt to different environments. This capacity allowed humans to spread all over our planet, occupying habitats as diverse as deserts, tropical forests or tundra regions. Interactions with the environment, climate, food and water availability shaped our evolution and define our survival. Essential to human life, oxygen availability also controls human dispersion and adaptation. For example, low oxygen availability can lead to physiological adaptations in populations living in highlands. Moreover, the consequences of differential oxygen availability (or even exposure to hypoxia) are evident in process as fine-tuned controlled as gene regulation. Physiological responses to fluctuations in oxygen availability are crucial already from the early days of life, since the human fetal environment is characterized by hypoxia. Hypoxia-Inducible Factors (HIFs) act as major regulators of pathways involved in glycolysis, erythropoiesis, angiogenesis, cell proliferation and stem cells function. Here we explore the physiological consequences of hypoxia in the human organism. In this sense, and considering the existence of HIF sequences in promoter regions of genes important to immune regulation, we hypothesize that exposure to induced hypoxia through the use of hypobaric chambers can be used as a complementary therapy to control chronic inflammation in several diseases characterized by systemic inflammatory conditions. Among these inflammatory conditions we highlight autoimmune diseases and chronic inflammation in HIV infected individuals under antiretroviral treatment. Several experiments, including arthritis animal models, the evaluation of athletes that already use hypobaric chambers to induce erythropoiesis, and the potential consequences of hypoxia as an immunotolerogenic inducer in the HIV infection context are approached and discussed here.

Keywords: HLA-G; Hypobaric hypoxia; Inflammation.