Dach1 transcription factor regulates the expression of peripheral node addressin and lymphocyte trafficking in lymph nodes

Arisa Shintani; Shoko Fukai; Reika Nobusawa; Kanako Taniguchi; Tomohiro Hatatani; Hayato Nagai; Tomohiro Sakai; Takuji Yoshimura; Masayuki Miyasaka; Haruko Hayasaka

doi:10.1016/j.crimmu.2022.08.008

Dach1 transcription factor regulates the expression of peripheral node addressin and lymphocyte trafficking in lymph nodes

Curr Res Immunol. 2022 Aug 21:3:175-185. doi: 10.1016/j.crimmu.2022.08.008. eCollection 2022.

Affiliations

¹ Faculty of Science & Engineering, Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka, Japan.
² WPI Immunology Frontier Research Center, Osaka University, 2-2, Yamada-oka, Suita, Osaka, Japan.
³ The Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan.

Abstract

Lymphocytes regulate the immune response by circulating between the vascular and lymphatic systems. High endothelial venules, HEVs, special blood vessels expressing selective adhesion molecules, such as PNAd and MAdCAM-1, mediate naïve lymphocyte migration from the vasculature into the lymph nodes and Peyer's patches. We have identified that DACH1 is abundantly expressed in developing HEV-type endothelial cells. DACH1 showed a restricted expression pattern in lymph node blood vessels during the late fetal and early neonatal periods, corresponding to HEV development. The proportion of MAdCAM-1⁺ and CD34⁺ endothelial cells is reduced in the lymph nodes of neonatal conventional and vascular-specific Dach1-deficient mice. Dach1-deficient lymph nodes in adult mice demonstrated a lower proportion of PNAd⁺ cells and lower recruitment of intravenously administered lymphocytes from GFP transgenic mice. These findings suggest that DACH1 promotes the expression of HEV-selective adhesion molecules and mediates lymphocyte trafficking across HEVs into lymph nodes.

Keywords: ECs, endothelial cells; Endothelial cell; HEV, High endothelial venules; ILNs, Inguinal lymph nodes; LNs, Lymph node; Lymph node; Lymphocyte; MAdCAM-1, mucosal addressin cell adhesion molecule-1; MLNs, Mesenteric lymph nodes; PNAd, peripheral node addressin; PPs, Peyer's patches; Trafficking; Transcription factor; mAb, monoclonal antibody.