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Catestatin (CST) is a bioactive cleavage product of the neuroendocrine prohormone chromogranin A (CgA). Recent findings show that CST can exert anti-inflammatory and antiadrenergic effects by suppressing the inflammatory actions of mammalian macrophages. However, recent findings also suggest that macrophages themselves are major CST producers. Here, we hypothesize that macrophages produce CST in an inflammation-dependent manner and thereby might self-regulate inflammation in an autocrine fashion. CST is associated with pathological conditions hallmarked by chronic inflammation, including autoimmune, cardiovascular, and metabolic disorders. Since intraperitoneal injection of CST in mouse models of diabetes and inflammatory bowel disease has been reported to be beneficial for mitigating disease, we posit that CST should be further investigated as a candidate target for treating certain inflammatory diseases., Competing Interests: Declaration of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In autoimmunity, aggressive immune responses are counteracted by suppressive rejoinders. For instance, FOXP3-expressing regulatory T cells (Tregs), have shown remarkable effects in limiting autoimmunity in preclinical models. However, early results from human Treg trials have not been as positive. Here, we highlight questions surrounding Treg transfers as putative treatments for autoimmunity. We discuss whether lack of antigenic recognition might be key to shifting cells from contributing to an aggressive autoresponse, to being part of a regulatory network. Moreover, we argue that identifying the physiological range of immunosuppression of Tregs might help potentiate their efficacy. We propose widening the view on immunoregulation by considering the participation of CD8 + Tregs in this process, which could have major implications in autoimmunity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Vascular permeability is a hallmark response to the main angiogenic factor VEGF-A and we have previously described a reduction of this response in Shb knockout mice. To characterize the molecular mechanisms responsible for this effect, endothelial cells were isolated from lungs and analyzed in vitro. Shb deficient endothelial cells exhibited less migration in a scratch wound-healing assay both under basal conditions and after vascular endothelial growth factor-A (VEGF-A) stimulation, suggesting a functional impairment of these cells in vitro. Staining for VE-cadherin and vascular endothelial growth factor receptor-2 (VEGFR-2) showed co-localization in adherens junctions and in intracellular sites such as the perinuclear region in wild-type and Shb knockout cells. VEGF-A decreased the VE-cadherin/VEGFR-2 co-localization in membrane structures resembling adherens junctions in wild-type cells whereas no such response was noted in the Shb knockout cells. VE-cadherin/VEGFR-2 co-localization was also recorded using spinning-disk confocal microscopy and VEGF-A caused a reduced association in the wild-type cells whereas the opposite pattern was observed in the Shb knockout cells. The latter expressed slightly more of cell surface VEGFR-2. VEGF-A stimulated extracellular-signal regulated kinase, Akt and Rac1 activities in the wild-type cells whereas no such responses were noted in the knockout cells. We conclude that aberrant signaling characteristics with respect to ERK, Akt and Rac1 are likely explanations for the observed altered pattern of VE-cadherin/VEGFR-2 association. The latter is important for understanding the reduced in vivo vascular permeability response in Shb knockout mice, a phenomenon that has patho-physiological relevance., (Copyright © 2012 Elsevier Inc. All rights reserved.)