부산대학교 도서관

CD[169.sup.+] macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD[169.sup.+] macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LT[beta]) receptor (R) signaling. In the absence or the reduced expression of either RANK or LT[beta]R, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LT[beta]R revealed that both receptors contribute equally to LN CD[169.sup.+] macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD[8.sup.+] T cells. Taken together, the data provide evidence that CD[169.sup.+] macrophage differentiation in LN and spleen requires dual signals from LT[beta]R and RANK with implications for the immune response. macrophages | RANK | lymphotoxin | lymph node | spleen