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CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis

Ifor R Williams1

  • 1Department of Pathology, Emory University School of Medicine, Whitehead 105D, 615 Michael Street, Atlanta, GA 30322, USA. irwilli@emory.edu

Annals of the New York Academy of Sciences
|October 24, 2006
PubMed

Insights

The chemokine receptor CCR6 and its ligand CCL20 are crucial for developing gut immune structures. Their interaction guides immune cell positioning, impacting IgA production and overall gut immunity.

Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • The CCR6 chemokine receptor is present on B cells, T cells, and dendritic cells (DCs) within the gut mucosal immune system.
  • CCL20, the sole ligand for CCR6, is produced by the follicle-associated epithelium (FAE) of Peyer's patches (PPs) and isolated lymphoid follicles (ILFs).
  • CCL20 expression in the intestinal epithelium can be induced by inflammatory signals, highlighting its dual role in homeostasis and inflammation.

Purpose of the Study:

  • To investigate the role of CCR6 and CCL20 interactions in the development and organization of gut-associated lymphoid tissues (GALTs).
  • To determine the impact of CCR6 deficiency on immune cell recruitment and the formation of intestinal lymphoid structures.
  • To assess the consequences of impaired GALTs development on mucosal immune responses, specifically IgA production.

Main Methods:

  • Analysis of CCR6 and CCL20 expression patterns in the gut mucosal immune system.
  • Utilizing CCR6 knockout mouse models to study the effects of receptor deficiency on lymphoid structure development.
  • Assessing immune cell populations and distribution within Peyer's patches, isolated lymphoid follicles, and cryptopatches.
  • Measuring IgA production in response to oral antigens in wild-type and CCR6-deficient mice.

Main Results:

  • CCL20 secreted by the FAE recruits CCR6-expressing B cells to PPs and ILFs.
  • CCR6-expressing lymphoid precursors in cryptopatches are recruited, contributing to ILF formation.
  • CCR6 knockout mice exhibit smaller PPs, reduced follicle numbers, and compromised ILF development.
  • Defects in mucosal inductive sites in CCR6-deficient mice lead to diminished IgA production against oral antigens.

Conclusions:

  • The CCR6-CCL20 axis is essential for the proper development and organization of intestinal lymphoid structures.
  • This chemokine interaction is critical for immune cell homing and the establishment of mucosal immune surveillance.
  • Dysregulation of CCR6-mediated pathways impairs IgA responses, underscoring their importance in gut immunity.

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