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

Tammy T Chang1, Isabelle Walther, Chai-Fei Li

  • 1Department of Surgery, University of California, San Francisco, CA, USA. tammy.chang@ucsf.edu

Journal of Leukocyte Biology
|July 4, 2012
PubMed

Insights

Microgravity impairs T cell activation by inhibiting key early gene transcription, posing risks for astronaut health during spaceflight. This research clarifies the molecular mechanisms behind this immunosuppression.

Area of Science:

  • Immunology
  • Space Biology
  • Molecular Biology

Background:

  • Spaceflight-induced immunosuppression is a significant challenge for long-term human space exploration.
  • T cell dysfunction is a key component of this immunosuppression, impacting host defense.
  • Understanding the molecular basis of impaired T cell activation in microgravity is crucial.

Purpose of the Study:

  • To determine if microgravity inhibits immediate early gene transcription in activated T cells.
  • To identify the specific genes and pathways affected by microgravity during T cell activation.
  • To establish microgravity as the causative factor for impaired T cell activation during spaceflight.

Main Methods:

  • Human T cells from four donors were activated on the International Space Station (ISS) under microgravity (μg) and a 1g control condition.
  • Cells were stimulated with Concanavalin A (Con A) and anti-CD28 antibodies.
  • Microarray gene expression analysis was performed after 1.5 hours of activation.

Main Results:

  • Microgravity and 1g conditions induced distinct global gene expression patterns in T cells.
  • 47 genes were significantly down-regulated in microgravity.
  • Key immediate early genes, including cREL, and their downstream targets (Rel/NF-κB, CREB, SRF) were inhibited in microgravity.
  • The TNF pathway was identified as a major early downstream effector pathway inhibited by microgravity.

Conclusions:

  • Microgravity directly inhibits the transactivation of critical immediate early genes in T cells.
  • This inhibition of early gene transcription is the causative factor for impaired T cell activation during spaceflight.
  • Impaired T cell function in microgravity could compromise host defense against infectious diseases in astronauts.

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