Differential regulation of CCL21 in lymphoid/nonlymphoid tissues for effectively attracting T cells to peripheral tissues

James C. Lo, Robert K. Chin, Youjin Lee, Hyung Sik Kang, Yang Wang, Joel V. Weinstock, Theresa Banks, Carl F. Ware, Guido Franzoso, Yang Xin Fu

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

CC chemokine ligand 21 (CCL21)/secondary lymphoid chemokine (SLC), a ligand for CC chemokine receptor 7 (CCR7), has been demonstrated to play a vital role in the homing and localization of immune cells to lymphoid tissues, but its role in nonlymphoid tissues largely remains undefined. Here, we provide evidence that CCL21 in lymphoid and nonlymphoid tissues is differentially regulated by lymphotoxin-dependent (LT-dependent) and -independent mechanisms, respectively. This differential regulation is due to the selective regulation of the CCL21-Ser/CCL21a but not the CCL21-Leu/CCL21b gene by the LT and noncanonical NF-κB pathways. This alternate pathway, not dependent on LT or lymphocytes, leading to constitutive expression of CCL21 in nonlymphoid tissues, is critical for the initial recruitment of T lymphocytes to peripheral effector sites. CCL21 expression is subsequently further enhanced in a LT-dependent fashion following airway challenge, potentially facilitating a positive feedback loop to attract additional CCR7+ effector cells. These findings establish an essential role for CCL21 in the recruitment of effector T cells to peripheral tissues and suggest that LT-dependent and -independent regulation of CCL21 plays a role in balancing the central and peripheral immune responses between lymphoid and nonlymphoid tissues.

Original languageEnglish (US)
Pages (from-to)1495-1505
Number of pages11
JournalJournal of Clinical Investigation
Volume112
Issue number10
DOIs
StatePublished - Nov 2003

ASJC Scopus subject areas

  • Medicine(all)

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    Lo, J. C., Chin, R. K., Lee, Y., Kang, H. S., Wang, Y., Weinstock, J. V., Banks, T., Ware, C. F., Franzoso, G., & Fu, Y. X. (2003). Differential regulation of CCL21 in lymphoid/nonlymphoid tissues for effectively attracting T cells to peripheral tissues. Journal of Clinical Investigation, 112(10), 1495-1505. https://doi.org/10.1172/JCI19188