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Key gravity-sensitive signaling pathways drive T cell activation

Boonyaratanakornkit, Jim Boonjit and Cogoli, Augusto and Li, Chai-Fei and Schopper, Thomas and Pippia, Proto Gavino and Galleri, Grazia and Meloni, Maria Antonia and Huges-Fulford, Millie (2005) Key gravity-sensitive signaling pathways drive T cell activation. The FASEB Journal, Vol. 19 (14), p. 2020-2022. eISSN 1530-6860. Article.

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DOI: 10.1096/fj.05-3778fje


Returning astronauts have experienced altered immune function and increased vulnerability to infection during spaceflights dating back to Apollo and Skylab. Lack of immune response in microgravity occurs at the cellular level. We analyzed differential gene expression to find gravity-dependent genes and pathways. We found inhibited induction of 91 genes in the simulated freefall environment of the random positioning machine. Altered induction of 10 genes regulated by key signaling pathways was verified using real-time RT-PCR. We discovered that impaired induction of early genes regulated primarily by transcription factors NF-κB, CREB, ELK, AP-1, and STAT after crosslinking the T-cell receptor contributes to T-cell dysfunction in altered gravity environments. We have previously shown that PKA and PKC are key early regulators in T-cell activation. Since the majority of the genes were regulated by NF-κB, CREB, and AP-1, we studied the pathways that regulated these transcription factors. We found that the PKA pathway was down-regulated in vg. In contrast, PI3-K, PKC, and its upstream regulator pLAT were not significantly down-regulated by vectorless gravity. Since NF-κB, AP-1, and CREB are all regulated by PKA and are transcription factors predicted by microarray analysis to be involved in the altered gene expression in vectorless gravity, the data suggest that PKA is a key player in the loss of T-cell activation in altered gravity.

Item Type:Article
ID Code:403
Uncontrolled Keywords:Immune response, gene expression, signal transduction, microarray, microgravity
Subjects:Area 05 - Scienze biologiche > BIO/09 Fisiologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze fisiologiche, biochimiche e cellulari
Publisher:The Federation of the American Societies for Experimental Biology
Additional Information:Pubblicato online il 6 ottobre 2005.
Deposited On:18 Aug 2009 10:02

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