A Functional Role for CCR6 on Proallergic T Cells in the Gastrointestinal Tract

Background & Aims

CCL20 is a chemokine that regulates the homeostatic and inflammatory trafficking of leukocytes to the small intestine and regulates the development of the gastrointestinal lymphoid architecture. T cells expressing T helper cell (Th) 2 cytokines are critical for experimental food allergy, and we hypothesized that CCL20 is involved in the localization of these cells to the gut.

Methods

We evaluated the role of CCR6 in allergic diarrhea induced by sensitization and oral challenge with ovalbumin (OVA) using CCR6^+/+ and CCR6^−/− mice.

Results

CCR6^−/− mice were protected from OVA-induced diarrhea but surprisingly were not impaired in mastocytosis or allergen-specific immunoglobulin E. CCR6^−/− mice were also protected from T cell-mediated diarrhea induced by anti-CD3 antibody. Allergic diarrhea was associated with an increased expression of Th2 cytokines within the intestinal mucosa that was significantly reduced in CCR6^−/− mice. Inhibition of lymphocyte homing by treatment with FTY720 did not impair allergic diarrhea, indicating that reactivation of T cells could occur locally within the small intestine. Finally, T-cell transfer studies demonstrated that CCR6 was required both on the transferred T cells and in the recipient mouse to manifest allergic disease in the gastrointestinal tract.

Conclusions

These studies highlight a mast cell– and immunoglobulin E–independent role for CCR6-bearing T cells in the pathogenesis of gastrointestinal allergic disease.

Abbreviations used in this paper: CFSE, carboxyfluoroscein succinimidyl ester, DC, dendritic cells, ELISA, enzyme-linked immunosorbent assay, IFN, interferon, Ig, immunoglobulin, IL, interleukin, mRNA, messenger RNA, MLN, mesenteric lymph node, NF, nuclear factor, OVA, ovalbumin, PBS, phosphate-buffered saline, PCR, polymerase chain reaction, RT, reverse-transcription, Th, T helper cell, TNF, tumor necrosis factor