No abstract

Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within the tissue parenchyma remain poorly defined. Here we studied IMs from murine lung, fat, heart, and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion (Slco2b1flox/DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.

Antigen-presenting dendritic cells often acquire foreign antigens in peripheral tissues such as the skin. Optimal encounter with naive T cells for the presentation of these antigens requires that the dendritic cells migrate to draining lymph nodes through lymphatic vessels. In this article, we review important aspects of what is known about dendritic-cell trafficking into and through lymphatic vessels to lymph nodes. We present these findings in the context of information about lymphatic-vessel biology. Gaining a better understanding of the crosstalk between dendritic cells and lymphatic vessels during the migration of dendritic cells to lymph nodes is essential for future advances in manipulating dendritic-cell migration as a means to fine-tune immune responses in clinical settings.

Langerhans cells (LCs) are the only dendritic cells of the epidermis and constitute the first immunological barrier against pathogens and environmental insults. The factors regulating LC homeostasis remain elusive and the direct circulating LC precursor has not yet been identified in vivo. Here we report an absence of LCs in mice deficient in the receptor for colony-stimulating factor 1 (CSF-1) in steady-state conditions. Using bone marrow chimeric mice, we have established that CSF-1 receptor-deficient hematopoietic precursors failed to reconstitute the LC pool in inflamed skin. Furthermore, monocytes with high expression of the monocyte marker Gr-1 (also called Ly-6c/G) were specifically recruited to the inflamed skin, proliferated locally and differentiated into LCs. These results identify Gr-1 hi monocytes as the direct precursors for LCs in vivo and establish the importance of the CSF-1 receptor in this process.Langerhans cells (LCs) are members of a family of highly specialized antigen-presenting cells called dendritic cells (DCs). Uniquely present in the epidermis, LCs form a tight cellular network that covers the entire body surface, constituting the first immunological barrier against the external environment. LCs are well equipped to ingest antigens present in the skin and to migrate to the regional lymph node in both steady-state and inflammatory conditions 1,2 . After being activated, LCs increase their expression of major histocompatibility complex (MHC) class II and costimulatory molecules 3 and migrate to T cell areas 2 of draining lymph nodes, where they secrete T cell-attractant chemokines 4 and interact with antigen-specific T cells. Whether migrating LCs serve mainly to carry antigens to blood-derived DCs in the draining lymph nodes or whether they directly prime or tolerize antigen-specific T cells is still debated 5-8 .Given their importance in skin immunity, the mobilization of LCs to draining lymph nodes and the subsequent replacement of migrating cells by newly differentiated LCs must be tightly regulated events. Indeed, LC homeostasis is differentially regulated in quiescent and Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/ Correspondance should be addressed to M.M. (miriam.merad@mssm.edu).