In 1971, Gabbiani and co-workers discovered and characterized the “modification of fibroblasts into cells which are capable of an active spasm” (contraction) in rat wound granulation tissue and, accordingly, named these cells ‘myofibroblasts’. Now, myofibroblasts are not only recognized for their physiological role in tissue repair but also as cells that are key in promoting the development of fibrosis in all organs. In this Cell Science at a Glance and the accompanying poster, we provide an overview of the current understanding of central aspects of myofibroblast biology, such as their definition, activation from different precursors, the involved signaling pathways and most widely used models to study their function. Myofibroblasts will be placed into context with their extracellular matrix and with other cell types communicating in the fibrotic environment. Furthermore, the challenges and strategies to target myofibroblasts in anti-fibrotic therapies are summarized to emphasize their crucial role in disease progression.

SummaryOne would assume that the anti-inflammatory activity of α1-anti-trypsin (AAT) is the result of inhibiting neutrophil enzymes. However, AAT exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. Targets outside the serineprotease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade AAT, is over-emphasized. Non-obvious developments in the understanding of AAT biology disqualify it from being a straightforward anti-inflammatory agent: AAT does not block dendritic cell activities, nor does it promote viral and tumour susceptibilities, stunt B lymphocyte responses or render treated patients susceptible to infections; accordingly, outcomes of elevated AAT do not overlap those attained by immunosuppression. Aside from the acutephase response, AAT rises during the third trimester of pregnancy and also in advanced age. At the molecular level, AAT docks onto cholesterol-rich lipid-rafts and circulating lipid particles, directly binds interleukin (IL)-8, ADAM metallopeptidase domain 17 (ADAM17) and danger-associated molecular pattern (DAMP) molecules, and its activity is lost to smoke, high glucose levels and bacterial proteases, introducing a novel entity -'relative AAT deficiency'. Unlike immunosuppression, AAT appears to help the immune system to distinguish between desired responses against authentic threats, and unwanted responses fuelled by a positive feedback loop perpetuated by, and at the expense of, inflamed injured innocent bystander cells. With a remarkable clinical safety record, AAT treatment is currently tested in clinical trials for its potential benefit in a variety of categorically distinct pathologies that share at least one common driving force: cell injury.

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Successful tissue repair after injury requires the complex interplay of multiple cell types in different activation states in the context of an extracellular matrix (ECM) with changing compositional and mechanical properties. Normal repair occurs in a highly regulated sequence of overlapping phases comprising hemostasis, inflammation, proliferation, remodeling, and maturation. 1,2 With breached or leaky vasculature, platelets exit the bloodstream and create a provisional ECM that serves as initial scaffold for immune cells and growth factors.Mast cells are early responders, followed by neutrophils that fight invading microorganisms and create a local environment of cytokines and hypoxia that stimulate the recruitment and/or activation of macrophages. While clearing wound tissue from debris and dead cells,