Maha Fahad Alenazy1,2, Fatemeh Saheb Sharif-Askari3, Mohammed S El-Wetidy4, Narjes Saheb Sharif-Askari3, Ibrahim Yaseen Hachim3,5, Mohammad-Hani Temsah1, Basema Saddik3,6, Roua Al-Kufaidy7, Maha A Omair8, Yasser A Alshawakir9, Amany Adulgadel Fathaddin10,11, Suad Hannawi12, Qutayba Hamid3,5,13, Mohammed A Omair14, Saleh Al-Muhsen1,11,15, Rabih Halwani1,3,5. 1. Department of Pediatrics, Immunology Research Lab, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 2. Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 3. Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. 4. College of Medicine Research Center, King Saud University, Riyadh, Saudi Arabia. 5. Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. 6. Department of Family and Community Medicine, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. 7. Prince Naif Center for Immunology Research and Asthma Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 8. Department of Statistics and Operations Research, College of Science, King Saud University, Riyadh, Saudi Arabia. 9. Experimental Surgery and Animal Lab, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 10. Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 11. King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia. 12. Department of Medicine, Ministry of Health and Prevention, Dubai, United Arab Emirates. 13. Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada. 14. Department of Medicine, Rheumatology Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 15. Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Abstract
BACKGROUNDS: Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. METHODS: Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay. RESULTS: Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice. CONCLUSIONS: These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.
BACKGROUNDS: Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. METHODS: Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay. RESULTS: Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice. CONCLUSIONS: These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.
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