Overlapping roles of CXCL13, interleukin 7 receptor alpha, and CCR7 ligands in lymph node development.
Lymphoid tissue development is associated with local accumulation of CD4+ CD3- IL-7R alpha hi hematopoietic cells that deliver lymphotoxin (LT)alpha 1 beta 2 signals to resident stromal cells. Previous studies have established an important role for CXCL13 ( BLC) in the development of Peyer's patches (PP) and some peripheral lymph nodes (LNs), but the chemokine requirements for several LN types, including mesenteric LNs, remain undefined. Using CXCL13-/- mice that additionally carry the paucity of LN T cell mutation (plt/plt), we discovered that CCR7 ligands function in peripheral LN development. We also tested for a genetic interaction during LN development between CXCL13 and a cytokine receptor required in PP development, IL-7R alpha. Mice deficient for both CXCL13 and IL-7R alpha displayed a striking absence of LNs, including mesenteric LNs. These data extend the role of CXCL13 to the development of all LNs and establish a previously unappreciated role for IL-7R alpha in this process. Both circulating and LN CD4+ CD3- IL-7R alpha hi cells are shown to express LT alpha 1 beta 2 in an IL-7R alpha-dependent manner. Furthermore, CXCL13 was found to be sufficient to mediate CD4+ CD3- IL-7R alpha hi cell recruitment in vivo to an ectopic site. These findings indicate that CXCL13 and CCR7 ligands promote accumulation of CD4+ CD3- IL-7R alpha hi cells, delivering IL-7R alpha-dependent LT alpha 1 beta 2 signals critical for LN development.[1]References
- Overlapping roles of CXCL13, interleukin 7 receptor alpha, and CCR7 ligands in lymph node development. Luther, S.A., Ansel, K.M., Cyster, J.G. J. Exp. Med. (2003) [Pubmed]
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