Susanne Heinzel

Functional immune profiling reveals CD4 + T cell dysregulation in coeliac disease

Anthony J. Farchione, HoChan Cheon, David Vremec, Julika Neumann et autres

Abstract T cells integrate signals from antigen and costimulatory receptors to calibrate response magnitude and quality, with genetically encoded programs shaping activation thresholds for immune tolerance and feedback regulation. Coeliac disease (CeD) is an autoimmune disorder with well‐defined genetic risk and immune …

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Control of antibody class switch recombination by quantitative integration of antigen signaling

Matthew C Wierzbowski, HoChan Cheon, Ken R. Duffy, Susanne Heinzel et autres

Immunoglobulin class switch recombination by B lymphocytes requires the simultaneous expression of activation-induced cytidine deaminase (AID) and noncoding germline transcripts (GLT). Expression of both components is controllable through cytokine signalling and arise through stochastic mechanisms linked to cell division that can be …

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Functional immune profiling reveals CD4 + T cell dysregulation associated with coeliac disease

Anthony J. Farchione, HoChan Cheon, David Vremec, Julika Neumann et autres

Abstract T cells integrate signals from antigen and co-stimulatory receptors to calibrate the strength and quality of their responses. This signal integration is influenced by genetic background, which can modulate thresholds for immune tolerance and strength of responses to threat. Celiac disease …

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Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses

John E. La Marca, Brandon J. Aubrey, Bruce Yang, Catherine W.T. Chang et autres

Whole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that impact responses of malignant cells to anti-cancer agents. Applying this methodology to lymphoma cells, we conducted a genome-wide screen to identify novel inhibitors of …

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Programmed death receptor 1 (PD‐1) ligand Fc fusion proteins reduce T‐cell proliferation in vitro independently of PD‐1

Melissa Biemond, David Vremec, Daniel H.D. Gray, Philip D. Hodgkin et autres

Abstract Programmed death receptor 1 (PD‐1) is an inhibitory receptor on T cells shown to restrain T‐cell proliferation. PD‐1 immune checkpoint blockade has emerged as a highly promising approach in cancer treatment. Much of our understanding of the function of PD‐1 is …

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Molecular control of the lymphocyte death timer

Michelle Ruhle, Evan A. Thomas, Edward Dann, Nicole Gottscheber et autres

ABSTRACT When stimulated, individual lymphocytes program times for division and death that are inherited within families, revealing a common timing mechanism transmitted over generations. Here we describe a threshold-based mechanism for the time to die. By comparing protein levels in control and …

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Survival and division fate programs are preserved but retuned during the naïve to memory CD8+ T‐cell transition

Susanne Heinzel, HoChan Cheon, Gabrielle T. Belz, Philip D. Hodgkin

Abstract Memory T cells are generated from naïve precursors undergoing proliferation during the initial immune response. Both naïve and memory T cells are maintained in a resting, quiescent state and respond to activation with a controlled proliferative burst and differentiation into effector …

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Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses

Marco J. Herold, John E. La Marca, Brandon J. Aubrey, Bruce Yang et autres

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Lineage tracing reveals B cell antibody class switching is stochastic, cell-autonomous, and tuneable

Miles B. Horton, HoChan Cheon, Ken R. Duffy, Daniel V. Brown et autres

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Cyton2: A Model of Immune Cell Population Dynamics That Includes Familial Instructional Inheritance

HoChan Cheon, Andrey Kan, Giulio Prevedello, Simone C. Oostindie et autres

Lymphocytes are the central actors in adaptive immune responses. When challenged with antigen, a small number of B and T cells have a cognate receptor capable of recognising and responding to the insult. These cells proliferate, building an exponentially growing, differentiating clone …

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Temporal analysis of Brd4 displacement in the control of B Cell survival, proliferation, and differentiation

IY Kong, JS Rimes, A Light, I Todorovski et autres

© 2020 The Authors JQ1 is a BET-bromodomain inhibitor that has immunomodulatory effects. However, the precise molecular mechanism that JQ1 targets to elicit changes in antibody production is not understood. Our results show that JQ1 induces apoptosis, reduces cell proliferation, and as …

Temporal analysis of Brd4 displacement in the control of B Cell survival, proliferation, and differentiation

IY Kong, JS Rimes, A Light, I Todorovski et autres

© 2020 The Authors JQ1 is a BET-bromodomain inhibitor that has immunomodulatory effects. However, the precise molecular mechanism that JQ1 targets to elicit changes in antibody production is not understood. Our results show that JQ1 induces apoptosis, reduces cell proliferation, and as …