Abstract
Many of the effector functions of antibodies rely on the binding of antibodies/immune complexes to cellular Fcγ receptors (FcγRs). Since the majority of innate immune effector cells express both activating and inhibitory Fc receptors, the outcome of the binding of immune complexes to cells of a given population is influenced by the relative affinities of the respective IgG subclasses to these receptors, as well as by the numbers of activating and inhibitory FcγRs on the cell surface. A group of immune cells that has come into focus more recently is the various subsets of tissue-resident macrophages. The central functions of FcγRs on tissue macrophages include the clearance of opsonized pathogens, the removal of small immune complexes from the circulation and the depletion of antibody-opsonized cells in the therapy of autoimmunity and cancer. Despite these essential functions of FcγRs on tissue-resident macrophages, an in-depth quantification of FcγRs is lacking. Thus, the aim of our current study was to quantify the various Fcγ receptors on macrophages in murine liver, lung, kidney, brain, skin and spleen. Our study identified a pronounced heterogeneity between FcγR expression patterns of the different tissue macrophages, which may reflect their specialized functions within their unique niches in different organ environments.
Highlights
Macrophages (MΦ) form a network of heterogeneous immunologic sentinels in all tissues, where they perform niche and tissue specific functions
Our study identified a striking organ-specific expression pattern of Fcγ receptors (FcγRs) on different tissue-resident macrophage subsets, providing the basis for understanding their activity in triggering local IgG subclass-dependent effector functions
Studies by many groups over the last decades have highlighted that organ-resident macrophages play a decisive role for tissue homeostasis and for the orchestration of tissuespecific immune responses
Summary
Macrophages (MΦ) form a network of heterogeneous immunologic sentinels in all tissues, where they perform niche and tissue specific functions. This involves classical immune functions like combating infections [1], the resolution of inflammation [2,3], surveillance against tumors [4,5] and mediation of antibody-dependent antitumoral [6]. Besides their immunologic functions, tissue-resident macrophages play pivotal roles in tissue homeostasis [8–10] and can modulate angiogenesis and lymphangiogenesis [11,12]. Macrophages are critically involved in various disorders, like cardiovascular [13] and pulmonary [14] diseases, type 2 diabetes [15] and cancer, where they can promote cancer initiation, malignant progression, tumor cell migration, in- and intravasation and the suppression of antitumor immunity (see, e.g., Reference [16]). Among the innate immune effector cells, macrophages express the broadest set of cell surface receptors, including pattern recognition receptors and complement and Fc receptors, allowing them to directly or indirectly detect pathogens
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