Camara, Abdouramane and Lavanant, Alice C. and Abe, Jun and Desforges, Henri Lee and Alexandre, Yannick O. and Girardi, Erika and Igamberdieva, Zinaida and Asano, Kenichi and Tanaka, Masato and Hehlgans, Thomas and Pfeffer, Klaus and Pfeffer, Sebastien and Mueller, Scott N. and Stein, Jens and Mueller, Christopher 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). ISSN 0027-8424, 1091-6490
Full text not available from this repository. (Request a copy)Abstract
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 (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 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 LT beta R and RANK with implications for the immune response.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LYMPHOTOXIN-BETA-RECEPTOR; SUBCAPSULAR SINUS MACROPHAGES; MARGINAL ZONE MACROPHAGES; B-CELLS; ANTIGEN; MAINTENANCE; ACTIVATION; MATURATION; INFECTION; SURFACE; macrophages; RANK; lymphotoxin; lymph node; spleen |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Feb 2024 08:39 |
| Last Modified: | 16 Feb 2024 08:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58012 |
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