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CCR6 identifies lymphoid tissue inducer cells within cryptopatches.

A Lügering¹, M Ross, M Sieker

¹Department of Medicine B, University of Münster, Münster, Germany. lugerin@uni-muenster.de

Clinical and Experimental Immunology

|February 13, 2010

Summary

Chemokine receptor CCR6 is vital for gut immunity, guiding specific immune cells to gut-associated lymphatic tissues. Its absence alters immune cell distribution and Peyer

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Area of Science:

Immunology
Gastroenterology
Cell Biology

Background:

The chemokine receptor CCR6 and its ligand CCL20 play roles in gut-associated lymphatic tissue (GALT) organization.
CCR6 is expressed on immune cells like dendritic cells, B cells, and T cells within the GALT.
CCL20 is produced by the follicle-associated epithelium and is essential for M cell development in Peyer's patches.

Purpose of the Study:

To investigate the role of CCR6 in identifying specific lymphocyte populations within gut lymphoid structures.
To characterize the function of CCR6-expressing lymphocytes in cryptopatches (CP).
To determine if CCR6 influences Notch molecule expression in lymphocytes and dendritic cells.

Main Methods:

Analysis of chemokine receptor expression on lineage-negative c-kit positive (lin(-) c-kit(+)) lymphocytes.
Comparison of CCR6-expressing cells within CP versus cells outside CP.
Assessment of CCR6-deficient mice for alterations in intestinal immunity.
Evaluation of Notch molecule and ligand expression in relation to CCR6 presence.

Main Results:

CCR6 specifically identifies lin(-) c-kit(+) lymphocytes located within cryptopatches (CP).
Lymphocytes outside CP express CXCR3 and possess distinct surface markers, suggesting at least two lin(-) c-kit(+) cell populations.
CCR6-deficient mice show increased intraepithelial lymphocytes, smaller Peyer's patches, and impaired CP to isolated lymphoid follicle (ILF) maturation.
CCR6 expression does not affect Notch molecule or ligand expression on the studied cells.
CCR6 identifies lymphocyte clusters in the human gut that resemble murine CP.

Conclusions:

CCR6 is a key marker for a specific subset of lymphocytes within gut cryptopatches.
The CCR6-CXCR3 axis may differentiate distinct lymphocyte populations within the gut immune system.
CCR6 plays a significant role in regulating lymphocyte localization and the development of gut-associated lymphoid structures.
CCR6 identifies potential human CP, highlighting its conserved role in gut immunity.