Ce mois-ci, la SFI et le Club Français des Jeunes Immunologistes mettent en avant l’article publié dans PNAS, de Alice Lavanant, qui fait sa thèse avec le Dr. Christopher Mueller, à l’Université de Starsourg. L’article sera publié sur le site de la SFI durant tout le mois d’Avril et concourra pour le prix du ” Meilleur article doctorant” au mois d’octobre prochain.

 

Journal PNAS 2022 Vol. 119 No. 3 e2108540119
Titre CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling
Auteurs A. Camara*, A. C. Lavanant*, J. Abe, H. Lee Desforges, Y. O. Alexandre, E. Girardi, Z. Igamberdieva, K. Asano, M. Tanaka, T. Hehlgans, K. Pfeffer, S. Pfeffer, S. N. Mueller, J. V. Stein, C. G. Mueller
Résumé
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.
https://immunology.fr/wp-content/uploads/formidable/21/immunology.fr-immunology.fr-camaralavanant-pnas-2022.pdf