Medical Treatment Can Unintentionally Alter the Regulatory T-Cell Compartment in Patients with Widespread Pathophysiologic Conditions

Abstract

Regulatory T cells (Tregs) are non-redundant mediators of immune tolerance that are critical to prevent autoimmune disease and promote an anti-inflammatory tissue environment. Many individuals experience chronic diseases and physiologic changes associated with aging requiring long-term medication. Unfortunately, adverse effects accompany every pharmacologic intervention and may affect overall outcomes. We focus on medications typically prescribed during the treatment of prevalent chronic diseases and disorders, including cardiovascular disease, autoimmune disease, and menopausal symptoms, that affect >200 million individuals in the United States. Increasing studies continue to report that treatment of patients with estrogen, metformin, statins, vitamin D, and tumor necrosis factor blockers are unintentionally modulating the Treg compartment. Effects of these medications likely comprise direct and/or indirect interaction with Tregs via other immune and parenchymal populations. Differing and sometimes opposing effects on the Treg compartment have been observed using the same medication. The length of treatment, dosing regimen and stage of disease, patient age, ethnicity, and sex may account for such findings and determine the specific signaling pathways affected by the medication. Enhancing the Treg compartment can skew the patient's immune system toward an anti-inflammatory phenotype and therefore could provide unanticipated benefit. Currently, multiple medicines prescribed to large numbers of patients influence the Treg compartment; however, how such effects affect their disease outcome and long-term health remains unclear.

Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma

“…The regulatory function of metformin on Tregs has not yet been clarified in obese asthma. In some immune-related inflammatory diseases, metformin inhibits the formation of the germ centre of the spleen and up-regulates Tregs to inhibit the formation of Teff cells, inhibiting the production of autoantibodies15 to exert an anti-inflammatory and anti-autoimmune role. Hence, it is vital and necessary to explore the mechanism by which metformin plays an anti-inflammatory role by increasing the Tregs in obese asthma.In summary, we found that (a) obese asthmatic mice showedmore severe airway inflammation; (b) metformin alleviated airway inflammation and increased Tregs in obese asthma.…”

Treg Cells in Ischemic Stroke: A Small Key to a Great Orchestrion

“…Примечательно, что ряд плейотропных биологически активных веществ, уже применяемых для лечения ишемического инсульта, также влияют и на Treg [96]. Например, к модуляторам Treg относятся мелатонин, эстроген, статины, витамин D и др.…”

“…Например, к модуляторам Treg относятся мелатонин, эстроген, статины, витамин D и др. [96]. Мелатонин привлекателен тем, что он давно известен в качестве нейропротектора, в том числе при лечении цереброваскулярной патологии [97].…”

T regulatory cells as a potential therapeutic target in psychosis? Current challenges and future perspectives

“…IL-6 blockade is not the only approach with indirect Treg-boosting effects. Others tested for such purpose include mTOR inhibitors (rapamycin, metformin), low-dose IL-2, TNFR2 agonists, rituximab, vitamin D, and others ( Copsel et al., 2020 ; Eggenhuizen et al., 2020 ; Fisher et al., 2019 ; Göschl et al., 2019 ; Rosenzwajg et al., 2019 ; Sharabi et al., 2018 ). Flow-cytometry, CyTOF and co-culture assays of Tregs during clinical trials could advance knowledge on novel mechanisms in psychosis, which we discuss in topic 4.…”