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Published on: July 25, 2016
Multiple interleukin-2 signaling pathways differentially regulated by microgravity
1Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
Defects in innate immunity have been demonstrated in astronauts after space flight. To investigate the role of microgravity on innate immune function, we evaluated NK and LAK activity of human PBMC stimulated with IL-2 under conditions of simulated microgravity, by using a rotating wall vessel (RWV) culture system. Under these conditions, both NK and LAK activity were generated at levels comparable to those found in static flask cultures. The phenotype of the activated PBMC was similar between the two culture conditions, with one notable exception: the IL-2 receptor alpha chain (CD25), which failed to be upregulated in simulated microgravity. To further investigate this change in IL-2 signaling, we examined the ability of IL-2 to induce secondary cytokines. The production of IFNgamma, IL-1beta, and TNFalpha was almost completely abrogated in the microgravity cultures, suggesting that the IL-2 signaling pathways leading to various IL-2-mediated effects are differentially regulated under bioreactor culture conditions.
Insights
Spaceflight impairs innate immunity. Simulated microgravity affected interleukin-2 (IL-2) signaling in immune cells, reducing secondary cytokine production despite comparable NK and LAK activity.
Area of Science:
- Immunology
- Space Medicine
- Cellular Biology
Background:
- Spaceflight is known to cause defects in innate immunity.
- Understanding the impact of microgravity on immune cells is crucial for astronaut health.
Purpose of the Study:
- To investigate the role of microgravity on innate immune function, specifically Natural Killer (NK) and Lymphokine-Activated Killer (LAK) cell activity.
- To evaluate the effects of simulated microgravity on immune cell signaling pathways.
Main Methods:
- Human peripheral blood mononuclear cells (PBMCs) were cultured under simulated microgravity using a rotating wall vessel (RWV) system.
- NK and LAK activity were assessed after stimulation with interleukin-2 (IL-2).
- Cell phenotype and secondary cytokine production (IFNgamma, IL-1beta, TNFalpha) were analyzed.
Main Results:
- NK and LAK activity were comparable in simulated microgravity and static cultures.
- Upregulation of the IL-2 receptor alpha chain (CD25) was significantly reduced in simulated microgravity.
- Production of secondary cytokines (IFNgamma, IL-1beta, TNFalpha) was abrogated under simulated microgravity conditions.
Conclusions:
- Simulated microgravity differentially regulates IL-2 signaling pathways in immune cells.
- Defects in IL-2 signaling may contribute to the immune system impairments observed after space flight.
- Further research is needed to understand the specific mechanisms involved in microgravity-induced immune dysregulation.
