cAIMPadministration in humanized mice induces a chimerization‐level‐dependentSTINGresponse

Autor:	Martin R. Jakobsen, Martin K. Thomsen, Lars Østergaard, Rikke Olesen, Katharina Mack, Christian Krapp, Jesper F Højen, Martin Tolstrup, Frederik Dagnæs-Hansen, Paul W. Denton, Anna H. F. Andersen, Kasper L Jønsson
Rok vydání:	2019
Předmět:	Immunology Spleen Inflammation Biology Mice Mice Inbred NOD innate immunology medicine Animals Humans Immunology and Allergy Innate immune system IFI16 Effector Membrane Proteins Nuclear Proteins Original Articles Phosphoproteins eye diseases Sting Haematopoiesis humanized mice medicine.anatomical_structure inflammation cGAMP Female Nucleotides Cyclic Stem cell medicine.symptom monocytes Signal Transduction
Zdroj:	Andersen, A H F, Olesen, R, Jønsson, K L, Højen, J F, Krapp, C, Mack, K, Thomsen, M K, Østergaard, L, Tolstrup, M, Dagnæs-Hansen, F, Jakobsen, M R & Denton, P W 2019, ' cAIMP administration in humanized mice induces a chimerization-level-dependent STING response ', Immunology, vol. 157, no. 2, pp. 163-172 . https://doi.org/10.1111/imm.13061 Andersen, A H F, Olesen, R, Jønsson, K L, Højen, J F, Krapp, C, Mack, K, Thomsen, M K, Østergaard, L, Tolstrup, M, Dagnaes-Hansen, F, Jacobsen, M R & Denton, P W 2019, ' cAIMP administration in humanized mice induces a chimerization-level-dependent STING response ' Immunology . https://doi.org/10.1111/imm.13061 Immunology
ISSN:	1365-2567 0019-2805
Popis:	It is well conceived that the STING signalling pathway is critical for generating a robust innate immune response to pathogens. Human and mouse STING signaling pathways are not identical, however. For example, mice lack IFI16 which has been proven important for the human STING pathway. Therefore, we investigated whether humanized mice are an appropriate experimental platform for exploring the human STING signaling cascade in vivo. We found that NOG mice reconstituted with human cord blood hematopoietic stem cells (humanized NOG mice) exhibit human STING signaling responses to an analog of the cyclic di-nucleotide cGAMP. There was an increase in the proportions of monocytes in the lungs of mice receiving cGAMP analog. The most robust levels of STING expression and STING-induced responses were observed in mice exhibiting the highest levels of human chimerization. Notably, differential levels of STING in lung versus spleen following cGAMP analog treatment suggest that there are tissue-specific kinetics of STING activation and/or degradation in effector versus inductive sites. We also examined the mouse innate immune response to cGAMP analog treatment. We detected that mouse cells in the immunodeficient NOG mice responded to the cGAMP analog and they do so with distinct kinetics from the human response. In conclusion, humanized NOG mice represent a valuable experimental model for examining in vivo human STING responses. This article is protected by copyright. All rights reserved.
Databáze:	OpenAIRE
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