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CCL17 and IL-10 as effectors that enable alternatively activated macrophages to inhibit the generation of classically

Tatsushi Katakura1, Masaru Miyazaki, Makiko Kobayashi

  • 1Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|January 22, 2004
PubMed

Insights

Alternatively activated macrophages (AAMphi) suppress the generation of classically activated macrophages (CAMphi). This inhibition is mediated by CCL17 and IL-10, crucial for innate immunity.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Classically activated macrophages (CAMphi) are key effector cells in innate immunity.
  • Alternatively activated macrophages (AAMphi) are prevalent in immunocompromised hosts, where CAMphi generation is impaired.

Purpose of the Study:

  • To investigate the mechanism by which AAMphi suppress the generation of CAMphi from resident macrophages (RMphi).

Main Methods:

  • AAMphi were isolated from mice post-thermal injury.
  • RMphi were stimulated with CpG DNA to induce CAMphi.
  • Dual-chamber Transwell assays and analysis of AAMphi culture supernatants were employed.

Main Results:

  • AAMphi and their culture supernatants inhibited CAMphi generation from RMphi, even with CpG DNA stimulation.
  • AAMphi culture supernatants contained IL-6, IL-10, CCL17, PGE(2), and TGF-beta.
  • CCL17 and IL-10 were identified as the key inhibitory factors, with antibody neutralization eliminating the suppressive effect.

Conclusions:

  • CCL17 and IL-10 secreted by AAMphi actively suppress the polarization of RMphi into CAMphi.
  • This mechanism highlights a novel regulatory pathway in macrophage activation relevant to immune responses.

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