Spaceflight Influences both Mucosal and Peripheral Cytokine Production in PTN-Tg and Wild Type Mice

Abstract

Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt) and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg) were examined using the novel Mouse Drawer System (MDS) aboard the International Space Station (ISS) over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2) and transforming growth factor-beta1 (TGF-β1) were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-β1 relative to ground controls. Total colonic TGF-β1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-β1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-β1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice.

A microRNA signature and TGF-β1 response were identified as the key master regulators for spaceflight response

“…Among in vivo studies, both short term and long-term flight data report changes in TGF-β mRNA levels in response to weightlessness and microgravity. During an 11-day space mission, rat skeletal muscle exhibited reduced TGF-β expression [ 41 ], and a 91-day mission aboard the ISS revealed lower TGF-β expression in colonic tissue, systemic lymph node, inguinal and brachial lymph nodes [ 42 ].…”

Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility

“…Spaceflight has been shown to increase the growth rate and virulence of multiple types of bacteria, but whether it affects commensal microbiota, a crucial arm of intestinal homeostasis, has not been thoroughly investigated (22). We present here that simulated microgravity could change the diversity of commensal bacteria within just 3 days, resulting in a dominant expansion of SFB.…”

“…Thus, it is expected that mucosal microbiota, coexisting with animals and playing an important role in normal development and health, are also influenced by microgravity (20, 21). However, the initial analysis of a limited number of mice aboard the International Space Station had not confirmed a significant change in the diversity of gut microflora (22).…”

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model

“…For instance, reduced length of villi and depth of crypts was found in rats that were flown on 12‐d Cosmos 2044 and Foton M3 missions (2, 3), and decreased mucin production of intestinal epithelial cells was shown in rats that were flown on the 19.5‐d Cosmos 605 mission (4). Colonic TGF‐α expression was altered in mice aboard the 13‐d STS‐135 or 91‐d International Space Station missions (5, 6). Using a well‐accepted, ground‐based spaceflight analog, the hindlimb unloading (HU) mouse model (7) found that simulated microgravity resulted in a transient increase in intestinal permeability, which is characterized by the elevation of circulating LPS and the activation of the innate immune system.…”