CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice Extract
Characteristic of allergic asthma, CD4+Th2 lymphocytes secrete Th2 cytokines, interleukin (IL)-4, IL-13, and IL-5 that mediate the inflammatory immune response. Surface expression of CD2 and its ligand, CD58, is increased on the monocytes and eosinophils of asthma patients, which correlate with elev...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00881/full |
| _version_ | 1818825940929609728 |
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| author | Tanwir Hashem Ananth K. Kammala Kanedra Thaxton Ryan M. Griffin Kellie Mullany Reynold A. Panettieri Hariharan Subramanian Rupali Das |
| author_facet | Tanwir Hashem Ananth K. Kammala Kanedra Thaxton Ryan M. Griffin Kellie Mullany Reynold A. Panettieri Hariharan Subramanian Rupali Das |
| author_sort | Tanwir Hashem |
| collection | DOAJ |
| description | Characteristic of allergic asthma, CD4+Th2 lymphocytes secrete Th2 cytokines, interleukin (IL)-4, IL-13, and IL-5 that mediate the inflammatory immune response. Surface expression of CD2 and its ligand, CD58, is increased on the monocytes and eosinophils of asthma patients, which correlate with elevated serum IgE levels, suggesting that CD2 may contribute to allergic airway inflammation. Using a murine model of asthma, we observed that house dust mice extract (HDME)-exposed Balb/c mice have increased airway hyperresponsiveness (AHR), lung inflammation, goblet cell hyperplasia, and elevated levels of Th2 cytokines in the lungs, as well as increased serum IgE levels as compared to the control mice. In contrast, with the exception of serum IgE levels, all the other parameters were significantly reduced in HDME-treated Cd2−/− mice. Interestingly, Il13 but not Il4 or Il5 gene expression in the lungs was dramatically decreased in HDME-exposed Cd2−/− mice. Of note, the gene expression of IL-13 downstream targets (Muc5b and Muc5ac) and high affinity IL-13Rα2 were upregulated in the lungs of HDME-exposed Balb/c mice but were significantly reduced in HDME-exposed Cd2−/− mice. Consistently, gene expression of microRNAs regulating mucin production, inflammation, airway smooth muscle cell proliferation and IL-13 transcripts were increased in the lungs of HDME-exposed Cd2−/− mice. Given the established role of IL-13 in promoting goblet cell hyperplasia, lung inflammation and AHR in allergic asthma, our studies reveal a unique role for CD2 in the regulation of Th2-associated allergic asthma. |
| first_indexed | 2024-12-19T00:19:45Z |
| format | Article |
| id | doaj.art-63d44d736e6740deae3394726fdde7bc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T00:19:45Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-63d44d736e6740deae3394726fdde7bc2022-12-21T20:45:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00881537877CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice ExtractTanwir Hashem0Ananth K. Kammala1Kanedra Thaxton2Ryan M. Griffin3Kellie Mullany4Reynold A. Panettieri5Hariharan Subramanian6Rupali Das7Department of Physiology, College of Natural Science, Michigan State University, East Lansing, MI, United StatesCollege of Human Medicine, Michigan State University, East Lansing, MI, United StatesDepartment of Physiology, College of Natural Science, Michigan State University, East Lansing, MI, United StatesDepartment of Physiology, College of Natural Science, Michigan State University, East Lansing, MI, United StatesDepartment of Chemical Engineering and Material Science, College of Engineering, Michigan State University, East Lansing, MI, United StatesRutgers Institute for Translational Medicine and Science, New Brunswick, NJ, United StatesCollege of Human Medicine, Michigan State University, East Lansing, MI, United StatesCollege of Human Medicine, Michigan State University, East Lansing, MI, United StatesCharacteristic of allergic asthma, CD4+Th2 lymphocytes secrete Th2 cytokines, interleukin (IL)-4, IL-13, and IL-5 that mediate the inflammatory immune response. Surface expression of CD2 and its ligand, CD58, is increased on the monocytes and eosinophils of asthma patients, which correlate with elevated serum IgE levels, suggesting that CD2 may contribute to allergic airway inflammation. Using a murine model of asthma, we observed that house dust mice extract (HDME)-exposed Balb/c mice have increased airway hyperresponsiveness (AHR), lung inflammation, goblet cell hyperplasia, and elevated levels of Th2 cytokines in the lungs, as well as increased serum IgE levels as compared to the control mice. In contrast, with the exception of serum IgE levels, all the other parameters were significantly reduced in HDME-treated Cd2−/− mice. Interestingly, Il13 but not Il4 or Il5 gene expression in the lungs was dramatically decreased in HDME-exposed Cd2−/− mice. Of note, the gene expression of IL-13 downstream targets (Muc5b and Muc5ac) and high affinity IL-13Rα2 were upregulated in the lungs of HDME-exposed Balb/c mice but were significantly reduced in HDME-exposed Cd2−/− mice. Consistently, gene expression of microRNAs regulating mucin production, inflammation, airway smooth muscle cell proliferation and IL-13 transcripts were increased in the lungs of HDME-exposed Cd2−/− mice. Given the established role of IL-13 in promoting goblet cell hyperplasia, lung inflammation and AHR in allergic asthma, our studies reveal a unique role for CD2 in the regulation of Th2-associated allergic asthma.https://www.frontiersin.org/article/10.3389/fimmu.2020.00881/fullasthmaTh2-allergic responsehouse dust mite extractcostimulatory moleculesCD2interleukin (IL)-13 |
| spellingShingle | Tanwir Hashem Ananth K. Kammala Kanedra Thaxton Ryan M. Griffin Kellie Mullany Reynold A. Panettieri Hariharan Subramanian Rupali Das CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice Extract Frontiers in Immunology asthma Th2-allergic response house dust mite extract costimulatory molecules CD2 interleukin (IL)-13 |
| title | CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice Extract |
| title_full | CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice Extract |
| title_fullStr | CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice Extract |
| title_full_unstemmed | CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice Extract |
| title_short | CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice Extract |
| title_sort | cd2 regulates pathogenesis of asthma induced by house dust mice extract |
| topic | asthma Th2-allergic response house dust mite extract costimulatory molecules CD2 interleukin (IL)-13 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00881/full |
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