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Supplemental material, sj-docx-4-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-1-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-2-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-3-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-2-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-4-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-3-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-5-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-1-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-5-tar-10.1177_17534666211039769 for Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke by Patrick F. Asare, Hai B. Tran, Plinio R. Hurtado, Griffith B. Perkins, Phan Nguyen, Hubertus Jersmann, Eugene Roscioli and Sandra Hodge in Therapeutic Advances in Respiratory Disease

Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC&ndash, derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC&ndash, derived EVs are a heterogeneous population, ranging in size from that of micro&ndash, vesicles (150 nm&ndash, 1 &mu, m) down to that of exosomes (60&ndash, 150 nm). Regarding their immunomodulatory functions, we found that upon isolation, the EVs (60&ndash, 150 nm) induced B cell proliferation and IgM antibody secretion. Analysis of the EV contents unexpectedly revealed the presence of BAFF, APRIL, IL&ndash, 6, and CD40L, all known to play a central role in B cell stimulation, differentiation, and humoral immunity. In regard to their effect on T cell functions, they resembled the function of mesenchymal stem cell (MSC)&ndash, derived EVs previously described, suppressing T cell response to activation. The finding that USC&ndash, derived EVs transport a potent bioactive cargo opens the door to a novel therapeutic avenue for boosting B cell responses in immunodeficiency or cancer.

The interplay between mesenchymal stem cells (MSCs) and immune cells has been studied for MSCs isolated from different tissues. However, the immunomodulatory capacity of urine stem cells (USCs) has not been adequately researched. The present study reports on the effect of USCs on peripheral blood lymphocytes. USCs were isolated and characterized before coculture with resting and with anti‐CD3/CD28 bead stimulated lymphocytes. Similarly to bone marrow mesenchymal stem cells (BM‐MSCs), USCs inhibited the proliferation of activated T lymphocytes and induced their apoptosis. However, they also induced strong activation, proliferation, and cytokine and antibody production by B lymphocytes. Molecular phenotype and supernatant analysis revealed that USCs secrete a range of cytokines and effector molecules, known to play a central role in B cell biology. These included B cell‐activating factor (BAFF), interleukin 6 (IL‐6) and CD40L. These findings raise the possibility of an unrecognized active role for kidney stem cells in modulating local immune cells., Kidney derived urine stem cells are equipped to provide B cells survival signals, promoting their activation, proliferation, and antibody production. Molecular phenotype and supernatant analysis revealed that USCs express the adhesion molecule ICAM‐1 and secrete B cell‐activating factor (BAFF), interleukin 6 (IL‐6) and CD40L, raising the possibility of an unrecognized active role for these cells in modulating local immune cells.

Objectives Regulatory T cells (Tregs) are a vital sub‐population of CD4+ T cells with major roles in immune tolerance and homeostasis. Given such properties, the use of regulatory T cells for immunotherapies has been extensively investigated, with a focus on adoptive transfer of ex vivo expanded natural Tregs (nTregs). For immunotherapies, induced Tregs (iTregs), generated in vitro from naïve CD4+ T cells, provide an attractive alternative, given the ease of generating cell numbers required for clinical dosage. While the combination of TGF‐β, ATRA and rapamycin has been shown to generate highly suppressive iTregs, the challenge for therapeutic iTreg generation has been their instability. Here, we investigate the impact of rapamycin concentrations and α‐CD3/CD28 bead ratios on human iTreg stability. Methods We assess iTregs generated with various concentrations of rapamycin and differing ratios of α‐CD3/CD28 beads for their differentiation, stability, expression of Treg signature molecules and T helper effector cytokines, and Treg‐specific demethylation region (TSDR) status. Results iTregs generated in the presence of TGF‐β, ATRA, rapamycin and a higher ratio of α‐CD3/CD28 beads were highly suppressive and stable upon in vitro re‐stimulation. These iTregs exhibited a similar expression profile of Treg signature molecules and T helper effector cytokines to nTregs, in the absence of TSDR demethylation. Conclusion This work establishes a method to generate human iTregs which maintain stable phenotype and function upon in vitro re‐stimulation. Further validation in pre‐clinical models will be needed to ensure its suitability for applications in adoptive transfer., Induced regulatory T cells are an attractive alternative for adoptive transfer in an allogeneic transplant setting. We report that rapamycin and abundant TCR stimulation are required to generate stable human induced regulatory T cells.