[Protective macrophages : New insights into the role of synovial macrophages in inflammatory joint diseases]. / Protektive Makrophagen : Neue Einblicke zur Rolle von Synovialmakrophagen bei entzündlichen Gelenkerkrankungen.

Macrophages are among the phylogenetically oldest cells of the immune system and are found in all tissues and organs. In addition to playing an important role in immune response against pathogenic microorganisms, these cells were previously described to play a vital role in chronic inflammatory diseases such as rheumatoid arthritis. Using novel techniques such as single-cell sequencing and advanced microscopy techniques it has now been shown that macrophages are far more versatile. Thus, these cells contribute considerably to tissue homeostasis and tissue regeneration. As each tissue has to fulfill special requirements, macrophages vary in their phenotype and function between organs. New data have now identified a specialised population of epithelioid macrophages that exert a protective and anti-inflammatory function in synovial tissue and prevent the initial onset as well as episodes of joint inflammation in rheumatoid arthritis.

Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes.

Clodronate liposomes (Clo-Lip) have been widely used to deplete mononuclear phagocytes (MoPh) to study the function of these cells in vivo. Here, we revisited the effects of Clo-Lip together with genetic models of MoPh deficiency, revealing that Clo-Lip exert their anti-inflammatory effects independent of MoPh. Notably, not only MoPh but also polymorphonuclear neutrophils (PMN) ingested Clo-Lip in vivo, which resulted in their functional arrest. Adoptive transfer of PMN, but not of MoPh, reversed the anti-inflammatory effects of Clo-Lip treatment, indicating that stunning of PMN rather than depletion of MoPh accounts for the anti-inflammatory effects of Clo-Lip in vivo. Our data highlight the need for a critical revision of the current literature on the role of MoPh in inflammation.

Synovial Macrophage and Fibroblast Heterogeneity in Joint Homeostasis and Inflammation.

The synovial tissue is an immunologically challenging environment where, under homeostatic conditions, highly specialized subsets of immune-regulatory macrophages and fibroblasts constantly prevent synovial inflammation in response to cartilage- and synovial fluid-derived danger signals that accumulate in response to mechanical stress. During inflammatory joint diseases, this immune-regulatory environment becomes perturbed and activated synovial fibroblasts and infiltrating immune cells start to contribute to synovial inflammation and joint destruction. This review summarizes our current understanding of the phenotypic and molecular characteristics of resident synovial macrophages and fibroblasts and highlights their crosstalk during joint homeostasis and joint inflammation, which is increasingly appreciated as vital to understand the molecular basis of prevalent inflammatory joint diseases such as rheumatoid arthritis.