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Morphological profiling of human T and NK lymphocytes by high-content cell imaging

Abstract : The immunological synapse is a complex structure that decodes stimulatory signals into adapted lymphocyte responses. It is a unique window to monitor lymphocyte activity because of development of systematic quantitative approaches. Here we demonstrate the applicability of high-content imaging to human T and natural killer (NK) cells and develop a pipeline for unbiased analysis of high-definition morphological profiles. Our approach reveals how distinct facets of actin cytoskeleton remodeling shape immunological synapse architecture and affect lytic granule positioning. Morphological profiling of CD8+ T cells from immunodeficient individuals allows discrimination of the roles of the ARP2/3 subunit ARPC1B and the ARP2/3 activator Wiskott-Aldrich syndrome protein (WASP) in immunological synapse assembly. Single-cell analysis further identifies uncoupling of lytic granules and F-actin radial distribution in ARPC1B-deficient lymphocytes. Our study provides a foundation for development of morphological profiling as a scalable approach to monitor primary lymphocyte responsiveness and to identify complex aspects of lymphocyte micro-architecture.
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Submitted on : Tuesday, November 23, 2021 - 12:39:20 PM
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Yolla German, Loan Vulliard, Anton Kamnev, Laurène Pfajfer, Jakob Huemer, et al.. Morphological profiling of human T and NK lymphocytes by high-content cell imaging. Cell Reports, Elsevier Inc, 2021, 36 (1), ⟨10.1016/j.celrep.2021.109318⟩. ⟨hal-03335500⟩



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