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Mice Deficient in NOX2 Display Severe Thymic Atrophy, Lymphopenia, and Reduced Lymphopoiesis in a Zymosan-Induced Model of Systemic Inflammation

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Abstract

Patients with chronic granulomatous disease (CGD) who have mutated phagocyte NADPH oxidase are susceptible to infections due to reduced reactive oxygen species production and exhibit autoimmune and inflammatory diseases in the absence of evident infection. Neutrophils and macrophages have been extensively studied since phagocyte NADPH oxidase is mainly found only in them, while the impact of its deficiency on lymphocyte cellularity is less well characterized. We showed herein a zymosan-induced systemic inflammation model that CGD mice deficient in the phagocyte NADPH oxidase gp91phox subunit (NOX2) exhibited more severe thymic atrophy associated with peripheral blood and splenic lymphopenia and reduced lymphopoiesis in the bone marrow in comparison with the wild-type mice. Conversely, the zymosan-exposed CGD mice suffered from more remarkable neutrophilic lung inflammation, circulating and splenic neutrophilia, and enhanced granulopoiesis compared with those in zymosan-exposed wild-type mice. Overall, this study provided evidence that NOX2 deficiency exhibits severe thymic atrophy and lymphopenia concomitant with enhanced neutrophilic inflammation in a zymosan-induced systemic inflammation model.

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Acknowledgment

We thank Dr. Mary C. Dinauer, Indiana University School of Medicine, for kindly providing the CGD mice. We thank Saori Takatori for the technical support.

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This work was supported in part by JSPS KAKENHI Grant number 17 K08126.

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  1. Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa, Yokohama, 236-0027, Japan

    Yu Sugimoto, Daiki Endo & Yasuaki Aratani

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Sugimoto, Y., Endo, D. & Aratani, Y. Mice Deficient in NOX2 Display Severe Thymic Atrophy, Lymphopenia, and Reduced Lymphopoiesis in a Zymosan-Induced Model of Systemic Inflammation. Inflammation 44, 371–382 (2021). https://doi.org/10.1007/s10753-020-01342-6

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