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Stepwise differentiation of follicular helper T cells reveals distinct developmental and functional states

Podesta MA, Cavazzoni CB, Hanson BL, Bechu ED, Ralli G, Clement RL, Zhang H, Chandrakar P, Lee JM, Reyes-Robles T, Abdi R, Diallo A, Sen DR, Sage PT.

Nature Communications. 2023. 14(1):7712.

In this article the Sage Lab assessed the development stages Tfh cells go through after initial differentiation to become effector Tfh cells. They found four distinct developmental stages in Tfh; Progenitor (Prog), Transitory (Trans), Fully Differentiated (Full) and Ex-Fully Differentiated (Ex). Authors also demonstrate intrinsic (FoxP1) and extrinsic (Tfr cells) factors controlling progression through these stages. This work demonstrates mechanisms controlling Tfh development and functionality and lay the framework for therapeutics to target individual Tfh stages to treat disease or enhance SARS-CoV-2 vaccines.

December, 2023

IL-21-producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts.

Zhang H, Cavazzoni CB, Podesta MA, Bechu ED, Ralli G, Chandrakar P, Lee JM, Sayin I, Tullius SG, Abdi R, Chong AS, Sage PT.

JCI Insight. 2023. Oct 23; 8(20)

In this article the Sage Lab studied developmental signals and functions of Tfh cells during allogeneic kidney transplantation. They found that Tfh undergo parallel development in LNs and kidney allografts. They also found that these Tfh cells control pathogenic B cell responses both within LNs and in kidney allografts themselves. This work provides rationale for targeting both systemic and kidney allograft B cell responses to prevent and treat antibody mediated rejection (ABMR) in the clinic.

December, 2023

Transcriptionally Distinct B Cells Infiltrate Allografts After Kidney Transplantation

Zhang, Hengcheng MD, PhD; Cavazzoni, Cecilia B. PhD; Hanson, Benjamin L.; Bechu, Elsa D.; Podestà, Manuel A. MD; Azzi, Jamil MD; Blazar, Bruce R. MD; Chong, Anita S. PhD; Kreisel, Daniel MD, PhD; Alessandrini, Alessandro PhD; Sage, Peter T. PhD

In this manuscript Dr. Sage’s team assessed the transcriptional programming and origins of intragraft B cells after kidney transplantation. They found that graft infiltrating B cells are innate-like transcriptionally and likely do not originate from lymph node germinal center B cells.

Transplantation 107(2):p e47-e57, February 2023. | DOI: 10.1097/TP.0000000000004398

May, 2023

Follicular T cells Optimize the Germinal Center Response to SARS-CoV-2 Protein Vaccination in Mice

Follicular T cells Optimize the Germinal Center Response to SARS-CoV-2 Protein Vaccination in Mice

Cavazzoni CB, Hanson BL, Podesta MA, Bechu ED, Clement RL, Zhang H, Daccache J, Reyes-Robles T, Hett EC, Vora KA, Fadeyi OO, Oslund RC, Hazuda DJ, Sage PT

Cell Reports, Feb. 2022

In this manuscript Dr. Sage’s team studied how follicular T cells control antibody responses during SARS-CoV-2 vaccination. Using genetic deletion studies and natural settings of aging they show that follicular T cells delicately balance affinity maturation and clonal expansion to optimize vaccine responses.

May, 2022

Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection

Paolo Fiorina et. al.

May, 2021

Patients with coronavirus disease 2019 (COVID-19) are reported to have a greater prevalence of hyperglycaemia. Cytokine release as a consequence of severe acute respiratory syndrome coronavirus 2 infection may precipitate the onset of metabolic alterations by affecting glucose homeostasis. Here we describe abnormalities in glycometabolic control, insulin resistance and beta cell function in patients with COVID-19 without any pre-existing history or diagnosis of diabetes, and document glycaemic abnormalities in recovered patients 2 months after onset of disease. In a cohort of 551 patients hospitalized for COVID-19 in Italy, we found that 46% of patients were hyperglycaemic, whereas 27% were normoglycaemic. Using clinical assays and continuous glucose monitoring in a subset of patients, we detected altered glycometabolic control, with insulin resistance and an abnormal cytokine profile, even in normoglycaemic patients. Glycaemic abnormalities can be detected for at least 2 months in patients who recovered from COVID-19. Our data demonstrate that COVID-19 is associated with aberrant glycometabolic control, which can persist even after recovery, suggesting that further investigation of metabolic abnormalities in the context of long COVID is warranted.

Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo

April, 2021

Solid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury.

Follicular T cells mediate donor-specific antibody and rejection after solid organ transplantation

Mostafa Mohammed et. al.

January, 2021

Following solid organ transplantation, a substantial proportion of chronic allograft loss is attributed to the formation of donor-specific antibodies (DSAs) and antibody-mediated rejection (AbMR).

A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant

Naoka Murakami et. al.

December, 2020

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020.

Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy

Liwei Jiang et. al.

November, 2020

Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined
with varying levels of success. Here, we describe a paradigmto control cancer growth that is based on
both direct tumor killing and the triggering of protective immunity.

Regulatory T cells engineered with TCR signaling–responsive IL-2 nanogels suppress alloimmunity in sites of antigen encounter

Siawosh K Eskandari et. al.

November, 2020

Adoptive cell transfer of ex vivo expanded regulatory T cells (Tregs) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such Treg therapies to the clinic has been slow.

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