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DOI10.1073/pnas.2108540119
CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling
Camara A.; Lavanant A.C.; Abe J.; Desforges H.L.; Alexandre Y.O.; Girardi E.; Igamberdieva Z.; Asano K.; Tanaka M.; Hehlgans T.; Pfeffer K.; Pfeffer S.; Mueller S.N.; Stein J.V.; Mueller C.G.
发表日期2022
ISSN0027-8424
卷号119期号:3
英文摘要CD169+ 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 CD169+ macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTβ) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTβR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTβR revealed that both receptors contribute equally to LN CD169+ 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 CD8+ T cells. Taken together, the data provide evidence that CD169+ macrophage differentiation in LN and spleen requires dual signals from LTβR and RANK with implications for the immune response. © This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
英文关键词Lymph node; Lymphotoxin; Macrophages; RANK; Spleen
语种英语
scopus关键词lymphotoxin beta receptor; receptor activator of nuclear factor kappa B; sialoadhesin; animal cell; animal experiment; Article; B lymphocyte; bone marrow cell; CD8+ T lymphocyte; cell differentiation; cell expansion; controlled study; cytotoxic T lymphocyte; down regulation; female; gene deletion; gene expression regulation; heterozygosity; immune response; LTbetaR signaling; lymph node; macrophage; male; marginal metallophilic macrophage; mouse; nonhuman; phenotype; protein protein interaction; RANK signaling; signal transduction; spleen
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/250892
作者单位CNRS, UPR 3572, University of Strasbourg, Strasbourg, 67000, France; Department of Oncology, Microbiology and Immunology, University of Fribourg, Fribourg, 1700, Switzerland; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; CNRS, Architecture et Reactivit e de l'ARN, UPR 9002, University of Strasbourg, Strasbourg, 67000, France; Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, 192-0392, Japan; Institute of Immunology, Regensburg Center for Interventional Immunology, University Medical Center of Regensburg, Regensburg, 93000, Germany; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Dusseldorf, Dusseldorf, 40000, Germany
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Camara A.,Lavanant A.C.,Abe J.,et al. CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling[J],2022,119(3).
APA Camara A..,Lavanant A.C..,Abe J..,Desforges H.L..,Alexandre Y.O..,...&Mueller C.G..(2022).CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling.Proceedings of the National Academy of Sciences of the United States of America,119(3).
MLA Camara A.,et al."CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling".Proceedings of the National Academy of Sciences of the United States of America 119.3(2022).
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