Intracellular Ca2+ Signaling and Calcium Release-Activated Calcium Modulator ORAI1 Are Associated With CD4+ T Lymphocytes in Dairy Cows
The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. Around the time of parturition, mobilization of body lipid and muscle helps compensate for the decrease in nutrient intake and the increased requirements of the mammary glan...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.835936/full |
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| author | Ming Li Bingbing Zhang Yufeng Yin Jianan Wen Jingjing Wang Yuxin He Qianming Jiang Juan J. Loor Shuang Wang Wei Yang Chuang Xu |
| author_facet | Ming Li Bingbing Zhang Yufeng Yin Jianan Wen Jingjing Wang Yuxin He Qianming Jiang Juan J. Loor Shuang Wang Wei Yang Chuang Xu |
| author_sort | Ming Li |
| collection | DOAJ |
| description | The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. Around the time of parturition, mobilization of body lipid and muscle helps compensate for the decrease in nutrient intake and the increased requirements of the mammary gland for lactation. An end-result of these processes is the marked increase in circulating concentrations of fatty acids (FA), which are a major risk factor for immune dysfunction. In food animal species such as dairy cows, any disturbance in nutritional or immunological homeostasis leads to deleterious feedback loops that can further risk health, efficiency of nutrient use, and compromise availability of safe and nutritious dairy foods for humans. Despite substantial progress with respect to regulation of innate immunity, such knowledge for adaptive immunity is scarce. To help bridge this gap in knowledge, we sought to study the role of calcium release-activated calcium modulator ORAI1 activation in T cells systemic immune function in vivo. CD4+ T cells were isolated from peripheral blood of dairy cows diagnosed as healthy or with ketosis, a common metabolic disorder of FA metabolism. Results revealed that levels of intracellular Ca2+ and reactive oxygen species (ROS) along with the abundance of store-operated Ca2+ entry (SOCE) moiety increased during ketosis. Further, plasma concentrations of inflammatory cytokines were elevated, the balance of Th17/Treg cells was disrupted, mitochondrial function impaired, and the abundance of mitophagy-related proteins in CD4+ T cells altered during ketosis. Molecular characterization of the direct effects of FA was evaluated in CD4+ T cells isolated from the spleen of 1-day-old calves. Enhanced supply of FA increased intracellular Ca2+ and ROS concentrations, upregulated the abundance of proteins associated with mitochondrial dynamics and ORAI1. Intermediates of mitophagy accumulated and the balance of Th17/Treg cells also was affected by the supply of FA. These negative effects were attenuated by silencing or inhibition of ORAI1 in CD4+ T cells. Together, data indicated that physiological states that lead to increases in systemic concentrations of FA could impact adaptive immunity negatively through ORAI1 regulated intracellular Ca2+, ROS balance, and increased effector functions of Th17 cells. |
| first_indexed | 2024-04-12T15:34:05Z |
| format | Article |
| id | doaj.art-fda10f3b7e9b4890862201290f178802 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T15:34:05Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fda10f3b7e9b4890862201290f1788022022-12-22T03:27:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.835936835936Intracellular Ca2+ Signaling and Calcium Release-Activated Calcium Modulator ORAI1 Are Associated With CD4+ T Lymphocytes in Dairy CowsMing Li0Bingbing Zhang1Yufeng Yin2Jianan Wen3Jingjing Wang4Yuxin He5Qianming Jiang6Juan J. Loor7Shuang Wang8Wei Yang9Chuang Xu10College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, ChinaMammalian NutriPhysio Genomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL, United StatesMammalian NutriPhysio Genomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL, United StatesCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, ChinaThe nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. Around the time of parturition, mobilization of body lipid and muscle helps compensate for the decrease in nutrient intake and the increased requirements of the mammary gland for lactation. An end-result of these processes is the marked increase in circulating concentrations of fatty acids (FA), which are a major risk factor for immune dysfunction. In food animal species such as dairy cows, any disturbance in nutritional or immunological homeostasis leads to deleterious feedback loops that can further risk health, efficiency of nutrient use, and compromise availability of safe and nutritious dairy foods for humans. Despite substantial progress with respect to regulation of innate immunity, such knowledge for adaptive immunity is scarce. To help bridge this gap in knowledge, we sought to study the role of calcium release-activated calcium modulator ORAI1 activation in T cells systemic immune function in vivo. CD4+ T cells were isolated from peripheral blood of dairy cows diagnosed as healthy or with ketosis, a common metabolic disorder of FA metabolism. Results revealed that levels of intracellular Ca2+ and reactive oxygen species (ROS) along with the abundance of store-operated Ca2+ entry (SOCE) moiety increased during ketosis. Further, plasma concentrations of inflammatory cytokines were elevated, the balance of Th17/Treg cells was disrupted, mitochondrial function impaired, and the abundance of mitophagy-related proteins in CD4+ T cells altered during ketosis. Molecular characterization of the direct effects of FA was evaluated in CD4+ T cells isolated from the spleen of 1-day-old calves. Enhanced supply of FA increased intracellular Ca2+ and ROS concentrations, upregulated the abundance of proteins associated with mitochondrial dynamics and ORAI1. Intermediates of mitophagy accumulated and the balance of Th17/Treg cells also was affected by the supply of FA. These negative effects were attenuated by silencing or inhibition of ORAI1 in CD4+ T cells. Together, data indicated that physiological states that lead to increases in systemic concentrations of FA could impact adaptive immunity negatively through ORAI1 regulated intracellular Ca2+, ROS balance, and increased effector functions of Th17 cells.https://www.frontiersin.org/articles/10.3389/fimmu.2022.835936/fullSOCEfatty acidsCD4+ T cellsketosisORAI1 |
| spellingShingle | Ming Li Bingbing Zhang Yufeng Yin Jianan Wen Jingjing Wang Yuxin He Qianming Jiang Juan J. Loor Shuang Wang Wei Yang Chuang Xu Intracellular Ca2+ Signaling and Calcium Release-Activated Calcium Modulator ORAI1 Are Associated With CD4+ T Lymphocytes in Dairy Cows Frontiers in Immunology SOCE fatty acids CD4+ T cells ketosis ORAI1 |
| title | Intracellular Ca2+ Signaling and Calcium Release-Activated Calcium Modulator ORAI1 Are Associated With CD4+ T Lymphocytes in Dairy Cows |
| title_full | Intracellular Ca2+ Signaling and Calcium Release-Activated Calcium Modulator ORAI1 Are Associated With CD4+ T Lymphocytes in Dairy Cows |
| title_fullStr | Intracellular Ca2+ Signaling and Calcium Release-Activated Calcium Modulator ORAI1 Are Associated With CD4+ T Lymphocytes in Dairy Cows |
| title_full_unstemmed | Intracellular Ca2+ Signaling and Calcium Release-Activated Calcium Modulator ORAI1 Are Associated With CD4+ T Lymphocytes in Dairy Cows |
| title_short | Intracellular Ca2+ Signaling and Calcium Release-Activated Calcium Modulator ORAI1 Are Associated With CD4+ T Lymphocytes in Dairy Cows |
| title_sort | intracellular ca2 signaling and calcium release activated calcium modulator orai1 are associated with cd4 t lymphocytes in dairy cows |
| topic | SOCE fatty acids CD4+ T cells ketosis ORAI1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.835936/full |
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