The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity

Tammy T. Chang, Isabelle Walther, Chai-Fei Li, Jim Boonyaratanakornkit, Grazia Galleri, Maria Antonia Meloni, Proto Pippia, Augusto Cogoli, Millie Hughes-Fulford

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

This study tested the hypothesis that transcription of immediate early genes is inhibited in T cells activated in μg. Immunosuppression during spaceflight is a major barrier to safe, long-term human space habitation and travel. The goals of these experiments were to prove that μg was the cause of impaired T cell activation during spaceflight, as well as understand the mechanisms controlling early T cell activation. T cells from four human donors were stimulated with Con A and anti-CD28 on board the ISS. An on-board centrifuge was used to generate a 1g simultaneous control to isolate the effects of μg from other variables of spaceflight. Microarray expression analysis after 1.5 h of activation demonstrated that μg- and 1g-activated T cells had distinct patterns of global gene expression and identified 47 genes that were significantly, differentially down-regulated in μg. Importantly, several key immediate early genes were inhibited in μg. In particular, transactivation of Rel/NF-κB, CREB, and SRF gene targets were downregulated. Expression of cREL gene targets were significantly inhibited, and transcription of cREL itself was reduced significantly in μg and upon anti-CD3/anti-CD28 stimulation in simulated μg. Analysis of gene connectivity indicated that the TNF pathway is a major early downstream effector pathway inhibited in μg and may lead to ineffective proinflammatory host defenses against infectious pathogens during spaceflight. Results from these experiments indicate that μg was the causative factor for impaired T cell activation during spaceflight by inhibiting transactivation of key immediate early genes.

Original languageEnglish (US)
Pages (from-to)1133-1145
Number of pages13
JournalJournal of Leukocyte Biology
Volume92
Issue number6
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Keywords

  • Immunosuppression
  • Microarray
  • Spaceflight
  • TNF

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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    Chang, T. T., Walther, I., Li, C-F., Boonyaratanakornkit, J., Galleri, G., Meloni, M. A., Pippia, P., Cogoli, A., & Hughes-Fulford, M. (2012). The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity. Journal of Leukocyte Biology, 92(6), 1133-1145. https://doi.org/10.1189/jlb.0312157