Il19-KO Mouse

Il19, a member of the IL-10 family of cytokines, is involved in diverse biological functions. It elicits host defense mechanisms, especially from epithelial cells during infections, and is essential for maintaining tissue epithelial layer integrity and homeostasis. It can promote innate immune responses and facilitate tissue-healing processes. The signaling of Il19 may be associated with the JAK1/STAT3 pathway [1,2].

In lung cancer, tumor cells can induce osteoclasts to secrete Il19, which then stimulates Il-20RB-expressing tumor cells via the JAK1/STAT3 signaling, promoting metastatic growth in bone, and blocking Il-20RB can suppress bone metastasis [2]. In atopic dermatitis, a novel Il19 + IGFL1 + keratinocyte subpopulation increases in lesions, which may disrupt the skin barrier, connect and magnify Th2 and Th17 inflammatory responses, and mediate skin pruritus [3]. DNA damage can enhance Il19 expression through JNK and cGAS-STING pathways, and Il19 is required for subsequent production of cytokines like IL-1, IL-6, and IL-8 [4].

In conclusion, Il19 is crucial for host defense, tissue homeostasis, and immune responses. Studies, such as those on lung cancer bone metastasis, atopic dermatitis, and DNA-damage-induced cytokine production, have revealed its role in disease-related biological processes. These findings contribute to understanding the functions of Il19 in disease development, potentially guiding future research and therapeutic strategies.

References:

1. Ouyang, Wenjun, Rutz, Sascha, Crellin, Natasha K, Valdez, Patricia A, Hymowitz, Sarah G. . Regulation and functions of the IL-10 family of cytokines in inflammation and disease. In Annual review of immunology, 29, 71-109. doi:10.1146/annurev-immunol-031210-101312. https://pubmed.ncbi.nlm.nih.gov/21166540/

2. He, Yunfei, Luo, Wenqian, Liu, Yingjie, Yao, Feng, Hu, Guohong. 2022. IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer. In The Journal of clinical investigation, 132, . doi:10.1172/JCI157917. https://pubmed.ncbi.nlm.nih.gov/36006737/

3. Zhou, Jie, Liang, Gaopeng, Liu, Lu, Wang, Li, Song, Zhiqiang. 2023. Single-cell RNA-seq reveals abnormal differentiation of keratinocytes and increased inflammatory differentiated keratinocytes in atopic dermatitis. In Journal of the European Academy of Dermatology and Venereology : JEADV, 37, 2336-2348. doi:10.1111/jdv.19256. https://pubmed.ncbi.nlm.nih.gov/37326015/

4. Small, Sara H, Tang, E Jessica, Ragland, Ryan L, Johnson, F Bradley, Brown, Eric J. 2021. Induction of IL19 expression through JNK and cGAS-STING modulates DNA damage-induced cytokine production. In Science signaling, 14, eaba2611. doi:10.1126/scisignal.aba2611. https://pubmed.ncbi.nlm.nih.gov/34932373/