Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases

Salminen, Antero

doi:10.1007/s00109-020-01988-7

Cited by 75 publications

(66 citation statements)

References 214 publications

(302 reference statements)

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“…To rule out the possibility that the observed anti-proliferative effect of zinc was the consequence of the production of immunosuppressive cytokines by T cells, we measured cytokine concentrations in the supernatants of freshly stimulated and pre-activated T cells following incubation with zinc aspartate. In this context, IL-1ra, latent TGF-β1, and IL-10 are best known for their immunosuppressive effects [ 21 , 22 ]. In addition, we measured the multifunctional cytokine IL-16 [ 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells

et al. 2021

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T cell activation mediates immunity to pathogens. On the flipside, T cells are also involved in pathological immune responses during chronic autoimmune diseases. We recently reported that zinc aspartate, a registered drug with high bioavailability, dose-dependently inhibits T cell activation and Th1/Th2/Th17 cytokine production of stimulated human and mouse T cells. To understand the suppressive effect of zinc on T cell function, we here investigated the influence of zinc aspartate on human T cells focusing on the secretion of immunosuppressive cytokines, induction of apoptosis, and caspase 3/7 activity. To this end, we monitored either freshly stimulated or pre-activated human T cells in the presence of zinc aspartate from 40–140 µM over a period of 72 h. Under both experimental conditions, we observed a dose-dependent suppression of human T cell proliferation. While IL-1ra, latent TGF-β1, and IL-10 were dose-dependently reduced, we, unexpectedly, detected elevated levels of IL-16 upon zinc supplementation. In addition, the number of cells with active caspase 3/7 and, consecutively, the amount of cells undergoing apoptosis, steadily increased at zinc aspartate concentrations exceeding 100 µM. Taken together, our findings suggest that zinc aspartate impairs T cell fitness and might be beneficial for the treatment of T cell-mediated autoimmune diseases.

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Section: Resultsmentioning

confidence: 99%

Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells

et al. 2021

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“…ageing, obesity, and diabetes, and their aberrant activities are present not only at the wound site, but also in bone marrow (BM) and blood circulation (2,(81)(82)(83). Alteration in the number and function of macrophage have been revealed in chronic wounds, which are closely related to hematopoietic disruption and particularly to myeloid skewing (67,(84)(85)(86).…”

Section: Systemic Factors Of Macrophage Dysfunctionmentioning

confidence: 99%

“…Chronic low-grade systemic inflammation is a common pathophysiological property of aging, obesity and diabetes (82,135,136). It is associated with a higher content of proinflammatory macrophages (137)(138)(139).…”

Section: Systemic Treatment Strategiesmentioning

confidence: 99%

Macrophage Related Chronic Inflammation in Non-Healing Wounds

et al. 2021

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Persistent hyper-inflammation is a distinguishing pathophysiological characteristic of chronic wounds, and macrophage malfunction is considered as a major contributor thereof. In this review, we describe the origin and heterogeneity of macrophages during wound healing, and compare macrophage function in healing and non-healing wounds. We consider extrinsic and intrinsic factors driving wound macrophage dysregulation, and review systemic and topical therapeutic approaches for the restoration of macrophage response. Multidimensional analysis is highlighted through the integration of various high-throughput technologies, used to assess the diversity and activation states as well as cellular communication of macrophages in healing and non-healing wound. This research fills the gaps in current literature and provides the promising therapeutic interventions for chronic wounds.

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“…Several reports demonstrate that persistent inflammation is associated with a compensatory anti-inflammatory response that could prevent excessive tissue damage by increasing immunosuppressive activity (217)(218)(219). The anti-inflammatory responses include the induction of myeloidbiassed haematopoietic stem cell differentiation, increased expansion of T reg cells and increased expression of antiinflammatory cytokines such as IL-10 and TGF-β (219).…”

Section: Do the Dysregulated Immune Features Associated With Diabetes Lead To A Severe Covid-19 Response?mentioning

confidence: 99%

Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

Roberts

Pritchard

Treweeke

et al. 2021

Front. Cardiovasc. Med.

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Meta-analyses have indicated that individuals with type 1 or type 2 diabetes are at increased risk of suffering a severe form of COVID-19 and have a higher mortality rate than the non-diabetic population. Patients with diabetes have chronic, low-level systemic inflammation, which results in global cellular dysfunction underlying the wide variety of symptoms associated with the disease, including an increased risk of respiratory infection. While the increased severity of COVID-19 amongst patients with diabetes is not yet fully understood, the common features associated with both diseases are dysregulated immune and inflammatory responses. An additional key player in COVID-19 is the enzyme, angiotensin-converting enzyme 2 (ACE2), which is essential for adhesion and uptake of virus into cells prior to replication. Changes to the expression of ACE2 in diabetes have been documented, but they vary across different organs and the importance of such changes on COVID-19 severity are still under investigation. This review will examine and summarise existing data on how immune and inflammatory processes interplay with the pathogenesis of COVID-19, with a particular focus on the impacts that diabetes, endothelial dysfunction and the expression dynamics of ACE2 have on the disease severity.

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Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases

Cited by 75 publications

References 214 publications

Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells

Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells

Macrophage Related Chronic Inflammation in Non-Healing Wounds

Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

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