Mast cells (MC) are a bone marrow-derived, long-lived, heterogeneous cellular population that function both as positive and negative regulators of immune responses. They are arguably the most productive chemical factory in the body and influence other cells through both soluble mediators and cell-to-cell interaction. MC are commonly seen in various tumors and have been attributed alternatively with tumor rejection or tumor promotion. Tumor-infiltrating MC are derived both from sentinel and recruited progenitor cells. MC can directly influence tumor cell proliferation and invasion but also help tumors indirectly by organizing its microenvironment and modulating immune responses to tumor cells. Best known for orchestrating inflammation and angiogenesis, the role of MC in shaping adaptive immune responses has become a focus of recent investigations. MC mobilize T cells and antigen-presenting dendritic cells. They function as intermediaries in regulatory T cells (Treg)-induced tolerance but can also modify or reverse Treg-suppressive properties. The central role of MC in the control of innate and adaptive immunity endows them with the ability to tune the nature of host responses to cancer and ultimately influence the outcome of disease and fate of the cancer patient.

Tsai et al. demonstrate that loss of Bim (BCL2L11) in myeloid cells in mice (LysMCreBimfl/fl) is sufficient to induce systemic autoimmunity. Kidney macrophages in LysMCreBimfl/fl mice possess a proinflammatory transcriptional signature and signal through TRIF to cause end-stage glomerulonephritis.

BackgroundThe risk for developing cardiovascular disease is greater in patients with rheumatoid arthritis (RA) than in the general population. While patients with RA also have dyslipidemia, the impact of dyslipidemia on the severity of inflammatory arthritis and associated cardiovascular disease is unclear. Currently, there are conflicting results regarding arthritis incidence in apolipoprotein E (ApoE) deficient mice, which spontaneously exhibit both hyperlipidemia and atherosclerosis. Here, we utilize a distinct approach to investigate the contribution of a hyperlipidemic environment on the development of arthritis and atherosclerosis in mice lacking ApoE.MethodsK/BxN serum transfer-induced arthritis (STIA) was assessed in C57BL/6 (control) and ApoE−/− mice using clinical indices and immunohistochemical staining. Ankle synoviums were processed for flow cytometry. Aortic atherosclerosis was quantitated using Sudan IV staining. Serum cholesterol and cytokine levels were determined via enzymatic and luminex bead-based assays, respectively.ResultsApoE−/− mice developed a sustained and enhanced semi-chronic inflammatory arthritis as compared to control mice. ApoE−/− mice had increased numbers of foamy macrophages, enhanced joint inflammation and amplified collagen deposition versus controls. The presence of arthritis did not exacerbate serum cholesterol levels or significantly augment the level of atherosclerosis in ApoE−/− mice. However, arthritic ApoE−/− mice exhibited a marked elevation of IL-6 as compared to non-arthritic ApoE−/− mice and arthritic C57BL/6 mice.ConclusionsLoss of ApoE potentiates a semi-chronic inflammatory arthritis. This heightened inflammatory response was associated with an increase in circulating IL-6 and in the number of foamy macrophages within the joint. Moreover, the foamy macrophages within the arthritic joint are reminiscent of those within unstable atherosclerotic lesions and suggest a pathologic role for foamy macrophages in propagating arthritis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0912-y) contains supplementary material, which is available to authorized users.

Systemic lupus erythematosus (SLE) is a chronic multi-factorial autoimmune disease initiated by genetic and environmental factors, which in combination trigger disease onset in susceptible individuals. Damage to the kidney as a consequence of lupus nephritis (LN) is one of the most prevalent and severe outcomes, as LN affects up to 60% of SLE patients and accounts for much of SLE-associated morbidity and mortality. As remarkable strides have been made in unlocking new inflammatory mechanisms associated with signaling molecules of programmed cell death pathways, this review explores the available evidence implicating the action of these pathways specifically within dendritic cells and macrophages in the control of kidney disease. Although advancements into the underlying mechanisms responsible for inducing cell death inflammatory pathways have been made, there still exist areas of unmet need. By understanding the molecular mechanisms by which dendritic cells and macrophages contribute to LN pathogenesis, we can improve their viability as potential therapeutic targets to promote remission.

Tumor growth requires interactions of tumor cells with a receptive and inductive microenvironment. Two major populations of tumor-infiltrating cells are considered to be essential for producing such a microenvironment: (1) proinflammatory cells that nurture the tumor with growth factors and facilitate invasion and metastasis by secreting proteases and (2) immune suppressive leukocytes including T-regulatory cells (Treg) that hinder tumor-specific CD8 T-cell responses, which otherwise could potentially reject the tumor. Among the proinflammatory cells, accumulation of mast cells (MCs) in human tumors is frequently recorded and was recently linked with poor prognosis. Causative links between mast cell infiltration and tumor progression can be deduced from animal studies. There is an interesting link between mast cells and Treg. The adoptive transfer of Treg from healthy syngeneic mice to mice susceptible to colon cancer suppresses focal mastocytosis and hinders tumor progression. Furthermore, T-cell-deficient mice susceptible to colon cancer show enhanced focal mastocytosis and tumor invasion. Here, we describe methods to assess MCs in mouse models of cancer and to investigate how MCs affect tumor epithelium. Additionally, we will detail methods used to investigate how T cells influence MCs and how MCs influence T cells.