Il5-KO Mouse

Il5, also known as interleukin-5, is a type-1 cytokine that is crucial for the initiation and sustenance of eosinophilic airway inflammation. It is central to the differentiation, migration, activation, and survival of eosinophils and also impacts the biological functions of mast cells, basophils, innate lymphoid cells, B cells, and epithelial cells. IL-5 is involved in type 2 inflammatory pathways, which are relevant in many allergic and eosinophilic diseases [1,3,5].

In the study of abdominal aortic aneurysm (AAA) using Rorafl/fl Il7rCre/+ (ILC2-deficient) and Icosfl-DTR-fl/+ Cd4Cre/+ (induced ILC2-depleted) mice, it was found that ILC2 protects mice from AAA formation via IL5 and eosinophils. IL5 from wild-type (WT) mice, but not from Il5-/-mice, induces EOS differentiation in bone-marrow cells from Rorafl/fl Il7rCre/+ mice. This shows that IL5 is essential in this protective mechanism in AAA development [2]. In Sharpin-deficient (Sharpin(cpdm)) mutant mice, treatment with anti-IL5 antibodies or breeding with IL5 null mice led to a significant reduction in eosinophils. However, the severity of dermatitis was not decreased, indicating that eosinophils may not be essential for dermatitis development in these mice, and eosinophils may have both pro-and anti-inflammatory roles in the skin [4].

In conclusion, Il5 plays a pivotal role in the innate and acquired immune response, especially in relation to eosinophilia. Mouse models, such as Il5 knockout and conditional knockout mice, have been instrumental in revealing its functions in diseases like abdominal aortic aneurysm and dermatitis. Understanding Il5's functions can potentially lead to better treatment strategies for eosinophilic-related diseases like asthma, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome [1,2,3,4,5].

References:

1. Mukherjee, Manali, Sehmi, Roma, Nair, Parameswaran. 2014. Anti-IL5 therapy for asthma and beyond. In The World Allergy Organization journal, 7, 32. doi:10.1186/1939-4551-7-32. https://pubmed.ncbi.nlm.nih.gov/25709744/

2. Zhang, Yuanyuan, Liu, Tianxiao, Deng, Zhiyong, Shi, Guo-Ping, Guo, Junli. 2023. Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2206958. doi:10.1002/advs.202206958. https://pubmed.ncbi.nlm.nih.gov/36592421/

3. Gevaert, Philippe, Han, Joseph K, Smith, Steven G, Chan, Robert, Bachert, Claus. 2022. The roles of eosinophils and interleukin-5 in the pathophysiology of chronic rhinosinusitis with nasal polyps. In International forum of allergy & rhinology, 12, 1413-1423. doi:10.1002/alr.22994. https://pubmed.ncbi.nlm.nih.gov/35243803/

4. Renninger, Matthew L, Seymour, Rosemarie E, Whiteley, Laurence O, Sundberg, John P, Hogenesch, Harm. 2009. Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice. In Experimental dermatology, 19, 252-8. doi:10.1111/j.1600-0625.2009.00944.x. https://pubmed.ncbi.nlm.nih.gov/19650867/

5. Takatsu, Kiyoshi, Nakajima, Hiroshi. 2008. IL-5 and eosinophilia. In Current opinion in immunology, 20, 288-94. doi:10.1016/j.coi.2008.04.001. https://pubmed.ncbi.nlm.nih.gov/18511250/