Effects of the Spaceflight Environment and Analog Clinical Models on Gastrointestinal Lymphatic and Immune Structure and Function

Abstract

Spaceflight exerts multiple environmental pressures upon astronauts causing both short and long-term physiological adaptations that may be debilitating and interfere with the ability for crewmembers to optimally function in space for long durations. Investigations characterizing the influences of space environmental factors such as microgravity and radiation have shown significant alterations in cardiovascular response, musculoskeletal function, behavioral health and performance, sensorimotor perceptions, and immunological sensitivity. However, there is a paucity of knowledge with regards to gastrointestinal function adaptations in response to either microgravity and/or space-relevant radiation exposure, as well as in the context of lymphatic structure/function and immunity. We compare and contrast these to the roles the lymphatic system plays in interstitial transport and immune components (such as cells and cytokines) in the context of clinical pathologies such as inflammatory bowel disease (IBD). Inflammatory bowel disease (IBD) affects approximately 1.6 million people in the United States with the incidence and prevalence increasing worldwide. IBD is considered an autoimmune condition in which the immune system mounts an attack against tissues within the digestive tract, with inflammation-induced lymphangiogenesis occurring in IBD as a compensatory response. It is currently unknown what drives these local lymphatic architecture changes and associated shifts in immune cytokine and cell adaptations at the local site or in association with lymphatic vessels downstream from the site of damage in IBD, microgravity, and/or radiation. The goals of the current project are to examine the lymphatic and immune structure and functional adaptations in different models of gastrointestinal inflammation relatable to clinical and space-relevant adaptive responses.