T cell regeneration: an update on progress and challenges

T cells play essential roles in antitumor therapy.Via gene engineering technique to enhance tumor-antigen specificity,patient peripheral blood-derived T cells(PBT)show encouraging clinical outcomes in treating certain blood malignancies.However,the high costs,functionality exhaustion,and disease-condition-dependent availability of PBT prompt the attempts of exploring alternative T cell sources.Theoretically,induced T cells from pluripotent stem cells(PSC)are ideal candidates that integrate plenty of advantages that primary T cells lack,including unlimited off-the-shelf cell source and precision gene editing feasibility.However,researchers are still struggling with developing a straightforward protocol to induce functional and immunocompetent human T cells from PSC.Based on stromal cell-expressing or biomaterial-presenting Notch ligands DLL1 or DLL4,natural and induced blood progenitors can differentiate further toward T lineage commitment.However,none of the reported T induction protocols has yet translated into any clinical application,signaling the existence of numerous technical barriers for regenerating T cells functionally matching their natural PBT counterparts.Alternatively,new approaches have been developed to repopulate induced T lymphopoiesis via in vivo reprogramming or transplanting induced T cell precursors.Here,we review the most recent progress in the T cell regeneration field,and the remaining challenges dragging their clinical applications.

Phosphorylation of PLIN3 by AMPK promotes dispersion of lipid droplets during starvation

Dear Editor,Lipid droplets(LDs)are dynamic lipid-storage organelles of storage depots and sources of essential substrates for myriad cellular processes and protect cells from lipotoxicity(Ohsaki et al.,2006).Disrupted LD and fat storage homeostasis has been linked to metabolic diseases such as atherosclerosis,obesity,and type II diabetes(Levin et al.,2001).Structurally,the core of neutral lipids in LDs is surroun ded by a phospholipid mono layer and coated with specific proteins(Storey et al.,2011).Perilipin family of proteins are the predominant LD-associated proteins.

Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients

Dear Editor,In 2019,a zoonotic coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified as the causative agent of Coronavirus Disease 2019(COVID-19).As of 8 June 2020,the World Health Organization(WHO)has reported 6,912,751 globally confirmed cases with 400,469 deaths.Although generally causes mild disease,SARS-CoV-2 infection can result in serious outcomes,including acute lung injury(ALI)and acute respiratory distress syndrome(ARDS),the leading cause of mortality in patients with comorbidities.Recent autopsy studies of COVID-19 patients revealed mononuclear infiltration and excessive production of mucus in the infected lung,especially in the damaged small airways and alveoli(Bian and Team,2020;Liu et al.,2020).

Pluripotent stem cell-derived CD 19-CAR iT cells effectively eradicate B-cell lymphoma in vivo

Chimeric antigen receptor T cell(CAR-T)therapy is one of the most promising approaches in cancer treatment.1 However,the limited availability of patient-derived T cells narrows its universal applicability.Thus,it is necessary to invent new methods to obtain alternative T-cell sources.Pluripotent stem cells(PSCs),which have unlimited culture potential and are amenable to gene editing,are ideal for generating induced T(iT)cells.

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.