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Mast cells (MCs) are evolutionarily ancient innate immune cells with important roles in protective immunity against bacteria, parasites, and venomous animals. They can be found in most organs of the body, where they also contribute to normal tissue functioning, for example by engaging in crosstalk with nerves. Despite this, they are most widely known for their detrimental roles in allergy, anaphylaxis, and atopic disease. Just like macrophages, mast cells were conventionally thought to originate from the bone marrow. However, they are already present in fetal tissues before the onset of bone marrow hematopoiesis, questioning this dogma. In recent years, our view of myeloid cell ontogeny has been revised. We now know that the first mast cells originate from progenitors made in the extra-embryonic yolk sac, and later get supplemented with mast cells produced from subsequent waves of hematopoiesis. In most connective tissues, sizeable populations of fetal-derived mast cells persist into adulthood, where they self-maintain largely independently from the bone marrow. These developmental origins are highly reminiscent of macrophages, which are known to have critical functions in development. Mast cells too may thus support healthy development. Their fetal origins and longevity also make mast cells susceptible to genetic and environmental perturbations, which may render them pathological. Here, we review our current understanding of mast cell biology from a developmental perspective. We first summarize how mast cell populations are established from distinct hematopoietic progenitor waves, and how they are subsequently maintained throughout life. We then discuss what functions mast cells may normally have at early life stages, and how they may be co-opted to cause, worsen, or increase susceptibility to disease., (© 2023 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.)

Macrophages are an integral part of all organs in the body, where they contribute to immune surveillance, protection, and tissue-specific homeostatic functions. This is facilitated by so-called niches composed of macrophages and their surrounding stroma. These niches structurally anchor macrophages and provide them with survival factors and tissue-specific signals that imprint their functional identity. In turn, macrophages ensure appropriate functioning of the niches they reside in. Macrophages thus form reciprocal, mutually beneficial circuits with their cellular niches. In this review, we explore how this concept applies to the spleen, a large secondary lymphoid organ whose primary functions are to filter the blood and regulate immunity. We first outline the splenic micro-anatomy, the different populations of splenic fibroblasts and macrophages and their respective contribution to protection of and key physiological processes occurring in the spleen. We then discuss firmly established and potential cellular circuits formed by splenic macrophages and fibroblasts, with an emphasis on the molecular cues underlying their crosstalk and their relevance to splenic functionality. Lastly, we conclude by considering how these macrophage-fibroblast circuits might be impaired by aging, and how understanding these changes might help identify novel therapeutic avenues with the potential of restoring splenic functions in the elderly., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lymph nodes (LNs) are secondary immune organs dispersed throughout the body. They are primarily composed of lymphocytes, "transient passengers" that are only present for a few hours. During this time, they extensively interact with a meshwork of stromal cells. Although these cells constitute less than 5% of all LN cells, they are integral to LN function: Stromal cells create a three-dimensional network that provides a rigid backbone for the transport of lymph and generates "roads" for lymphocyte migration. Beyond structural support, the LN stroma also produces survival signals for lymphocytes and provides nutrients, soluble factors, antigens, and immune cells collectively required for immune surveillance and the generation of adaptive immune responses. A unique feature of LNs is their ability to considerably and rapidly change size: the volume and cellularity of inflamed LNs can increase up to 20-fold before returning to homeostatic levels. This cycle will be repeated many times during life and is accommodated by stromal cells. The dynamics underlying this dramatic remodeling are subject of this review. We will first introduce the main types of LN stromal cells and explain their known functions. We will then discuss how these cells enable LN growth during immune responses, with a particular focus on underlying cellular mechanisms and molecular cues. Similarly, we will elaborate on stromal dynamics mediating the return to LN homeostasis, a process that is mechanistically much less understood than LN expansion., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue-resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self-maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue-specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue-resident macrophages and how they differ from freshly recruited short-lived monocyte-derived cells. We examine whether macrophage proliferation can be qualified as self-renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self-renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self-renewal could be exploited for therapeutic intervention of macrophage-mediated pathologies by selectively targeting freshly recruited or resident macrophages., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)