Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca2+ Influx in Nkx2-3 Knock-out Mice

Khanfar, Esam; Olasz, Katalin; Gábris, Fanni; Gajdócsi, Erzsébet; Botz, Bálint; Kiss, Tamás; Kugyelka, Réka; Berki, Tímea; Balogh, Péter; Boldizsár, Ferenc

doi:10.3390/ijms21176162

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Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca²⁺ Influx in Nkx2-3 Knock-out Mice

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Department of Immunology and Biotechnology, Medical School, University of Pécs, 7624 Pécs, Hungary

Lymphoid Organogenesis Research Group, János Szentágothai Research Centre, University of Pécs, 7624 Pécs, Hungary

Department of Medical Imaging, Medical School, University of Pécs, 7624 Pécs, Hungary

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Molecular Pharmacology Research Group, János Szentágothai Research Centre and Centre for Neuroscience, University of Pécs, 7624 Pécs, Hungary

⁵

Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, 7624 Pécs, Hungary

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(17), 6162; https://doi.org/10.3390/ijms21176162

Received: 23 July 2020 / Revised: 24 August 2020 / Accepted: 25 August 2020 / Published: 26 August 2020

(This article belongs to the Special Issue Research of Pathogenesis and Novel Therapeutics in Arthritis 2.0)

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Abstract

B cells play a crucial role in the pathogenesis of rheumatoid arthritis. In Nkx2-3-deficient mice (Nkx2-3^−/−) the spleen’s histological structure is fundamentally changed; therefore, B cell homeostasis is seriously disturbed. Based on this, we were curious, whether autoimmune arthritis could be induced in Nkx2-3^−/− mice and how B cell activation and function were affected. We induced arthritis with immunization of recombinant human proteoglycan aggrecan G1 domain in Nkx2-3^−/− and control BALB/c mice. We followed the clinical picture, characterized the radiological changes, the immune response, and intracellular Ca²⁺ signaling of B cells. Incidence of the autoimmune arthritis was lower, and the disease severity was milder in Nkx2-3^−/− mice than in control BALB/c mice. The radiological changes were in line with the clinical picture. In Nkx2-3^−/− mice, we measured decreased antigen-induced proliferation and cytokine production in spleen cell cultures; in the sera, we found less anti-CCP-IgG2a, IL-17 and IFNγ, but more IL-1β, IL-4 and IL-6. B cells isolated from the lymph nodes of Nkx2-3^−/− mice showed decreased intracellular Ca²⁺ signaling compared to those isolated from BALB/c mice. Our findings show that the transcription factor Nkx2-3 might regulate the development of autoimmune arthritis most likely through modifying B cell activation. View Full-Text

Keywords: autoimmune arthritis; Nkx2-3; B cell activation

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Khanfar, E.; Olasz, K.; Gábris, F.; Gajdócsi, E.; Botz, B.; Kiss, T.; Kugyelka, R.; Berki, T.; Balogh, P.; Boldizsár, F. Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca²⁺ Influx in Nkx2-3 Knock-out Mice. Int. J. Mol. Sci. 2020, 21, 6162. https://doi.org/10.3390/ijms21176162

AMA Style

Khanfar E, Olasz K, Gábris F, Gajdócsi E, Botz B, Kiss T, Kugyelka R, Berki T, Balogh P, Boldizsár F. Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca²⁺ Influx in Nkx2-3 Knock-out Mice. International Journal of Molecular Sciences. 2020; 21(17):6162. https://doi.org/10.3390/ijms21176162

Chicago/Turabian Style

Khanfar, Esam, Katalin Olasz, Fanni Gábris, Erzsébet Gajdócsi, Bálint Botz, Tamás Kiss, Réka Kugyelka, Tímea Berki, Péter Balogh, and Ferenc Boldizsár. 2020. "Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca²⁺ Influx in Nkx2-3 Knock-out Mice" International Journal of Molecular Sciences 21, no. 17: 6162. https://doi.org/10.3390/ijms21176162

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