Axl Is A Key Regulator Of Intestinal Gamma Delta T-Cell Homeostasis

Gut-homing gamma delta T cells are induced by chemokines and cell adhesion molecules and play a critical role in homeostasis and mucosal immunity; however, little is known regarding their upstream regulators. We investigated the role of Axl as a specific regulator of chemokines and cell adhesion molecule in the distribution of intestinal gamma delta T cells. The population of gamma delta T-cell receptor-positive cells including V gamma 1 and V gamma 7 subsets was remarkably increased in the intraepithelial lymphocytes of Axl(-/-) mice compared with those of wild-type (WT) mice. An increased number of migrated gamma delta T cells were observed in the coculture with intraepithelial cells from Axl(-/-) mice. The mRNA expression level of chemokine (C-C motif) ligand (CCL) 25 was specifically higher in the small intestine of Axl(-/-) mice than in WT mice. In adoptive transfer, the migration of both thymic and extrathymic gamma delta T cells was increased in Axl(-/-) mice. The activation of Axl signaling down-regulated CCL25 expression via ERK signaling pathway and reduced the population of gamma delta T cells. Systemic dissemination was suppressed in Axl(-/-) mice infected with Salmonella typhimurium. Thus, our findings suggest that Axl plays a critical role in regulating the migration of gamma delta T cells for the maintenance of homeostasis and bacterial resistance.