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Gene expression profiling identifies STAT3 as a novel pathway for immunomodulation by cholera toxin adjuvant

A Sjöblom-Hallén1, U Marklund, A Nerstedt

  • 1Department of Microbiology and Immunology, Institute of Biomedicine, Mucosal Immunobiology and Vaccine Center (MIVAC), Gothenburg, Sweden.

Mucosal Immunology
|April 9, 2010
PubMed

Insights

Cholera toxin (CT) regulates STAT3 in B cells, influencing immune responses. This provides a molecular mechanism for CT's dual pro- and anti-inflammatory effects as an adjuvant.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Cholera toxin (CT) exhibits both pro-inflammatory and anti-inflammatory activities.
  • CT is a potent immune adjuvant, necessitating investigation into its underlying molecular mechanisms.
  • Previous studies have yielded conflicting results regarding CT's immunomodulatory effects.

Purpose of the Study:

  • To identify genes involved in the pro- and anti-inflammatory functions of CT.
  • To elucidate the molecular mechanism by which CT influences B cell responses.
  • To reconcile the disparate findings on CT's adjuvant properties.

Main Methods:

  • Global gene expression analysis in mouse B cells treated with CT.
  • Investigation of signal transducer and activator of transcription (STAT)3 expression and activation in B cells (in vitro and in vivo).
  • Assessment of B cell responses to interleukin (IL)-6 and IL-10 following CT pre-exposure, including proliferation and cytokine production.

Main Results:

  • CT regulated fewer than 100 annotated genes in mouse B cells, including STAT3.
  • CT increased STAT3 expression and activation in a cAMP-dependent manner, independent of CTB.
  • CT-exposed B cells showed enhanced STAT3 activation by IL-6 and IL-10, leading to increased IgG1 and IgA production and altered IL-10 effects on LPS-stimulated B cells.

Conclusions:

  • CT modulates STAT3 signaling in B cells, providing a molecular basis for its dual immunomodulatory effects.
  • This study reconciles previous observations of CT's pro- and anti-inflammatory roles.
  • CT's adjuvant activity is linked to its influence on STAT3 pathways and subsequent B cell responses.

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