Mechano-Immunomodulation in Space: Mechanisms Involving Microgravity-Induced Changes in T Cells

Abstract

Of the most prevalent issues surrounding long-term spaceflight, the sustainability of human life and the maintenance of homeostasis in an extreme environment are of utmost concern. It has been observed that the human immune system is dysregulated in space as a result of gravitational unloading at the cellular level, leading to potential complications in astronaut health. A plethora of studies demonstrate intracellular changes that occur due to microgravity; however, these ultimately fall short of identifying the underlying mechanisms and dysfunctions that cause such changes. This comprehensive review covers the changes in human adaptive immunity due to microgravity. Specifically, there is a focus on uncovering the gravisensitive steps in T cell signaling pathways. Changes in gravitational force may lead to interrupted immune signaling cascades at specific junctions, particularly membrane and surface receptor-proximal molecules. Holistically studying the interplay of signaling with morphological changes in cytoskeleton and other cell components may yield answers to what in the T cell specifically experiences the consequences of microgravity. Fully understanding the nature of this problem is essential in order to develop proper countermeasures before long-term space flight is conducted.

Potential Biomarkers of Resilience to Microgravity Hazards in Astronauts

“…One of the potential consequences of microgravity-induced immune dysregulation is the development of hypersensitivity reactions [ 37 ]. Hypersensitivity reactions are exaggerated or inappropriate immune responses to specific antigens, which can manifest as allergic reactions, autoimmune disorders, or other inflammatory conditions [ 38 , 39 ]. In the context of spaceflight, hypersensitivity reactions may be triggered by factors such as altered antigen presentation, changes in cytokine profiles, and increased oxidative stress [ 36 ].…”

Homo sapiens—A Species Not Designed for Space Flight: Health Risks in Low Earth Orbit and Beyond, Including Potential Risks When Traveling beyond the Geomagnetic Field of Earth

“…Interestingly, this heterogeneity may be silent on Earth, but could potentially contribute to disease development, particularly in conditions arising during aging; The gut microbiome also appears to be altered during space flight and when living in LEO, a finding that could also lead to alterations in the relationship with the host and that may require separate countermeasures, such as prebiotics [ 101 ]; Diseases arising during space flight or when living in LEO may not present with the same symptoms and may not respond to interventions the same as on Earth, since the set point for the integrated biological systems would be altered. While not discussed, the immune system of astronauts and animal models is altered during space flight [ 102 , 103 , 104 ], a factor that may further complicate disease development and intervention efficacy and one that may require specific countermeasures [ 105 ]; Space flight or living in LEO appears to lead to epigenetic changes in astronauts [ 106 ]. While some changes were observed to be reversable once returning to Earth, this may not be the case for all of the changes, and the changes may continue with prolonged time in space; As a number of system stressors arise from living in LEO, the impact on systems such as the brain and cardiovascular systems is complex.…”

“…Diseases arising during space flight or when living in LEO may not present with the same symptoms and may not respond to interventions the same as on Earth, since the set point for the integrated biological systems would be altered. While not discussed, the immune system of astronauts and animal models is altered during space flight [ 102 , 103 , 104 ], a factor that may further complicate disease development and intervention efficacy and one that may require specific countermeasures [ 105 ];…”

Morphofunctional Changes in Peripheral Immune Organs in Space Flight and Weightlessness Modeling

“…[13] приводят данные об изменениях протеина p53 и показывают значительное усиление проявлений апоптоза в иммунных клетках. Имеются сведения [28,59] об увеличении экспрессии рецептора апоптоза Fas/APO-1(CD 95). Усиление процессов апоптоза лимфоцитов подтверждается и результатами исследования фрагментации ДНК, исследованиями полимеразы и экспрессии гена p53.…”

“…В последующем [62] автор выдвигает предположение, что основной причиной нарушения иммунитета в космическом полете является снижение уровня цитокина TNF-α. Данные о подавлении активности иммунной системы, прежде всего Т-системы в условиях невесомости приводятся в обзоре [28], что по мнению авторов связано с нарушениями основных путей транскрипции, таких как IL-2: PKC/NF-KB, Ras/Ap-1 и кальциневрин/NFAT. Важной сигнальной молекулой, выделяемой Т-лимфоцитами при активации, является INFγ, основной путь для активации макрофагов.…”