Il19-KO Mouse

Il19, a cytokine, is a member of the IL-10 family [1]. The IL-10 family cytokines are crucial for maintaining tissue epithelial layer integrity and homeostasis, and can promote innate immune responses to limit damage from infections and facilitate tissue-healing [1]. IL-19 was previously regarded as an anti-inflammatory cytokine, but has also been proposed as an immunoregulatory cytokine [9].

In lung cancer, osteoclasts secrete IL-19, which stimulates IL-20RB-expressing tumor cells to activate the JAK1/STAT3 signaling pathway, promoting metastatic growth in bone [2]. In atopic dermatitis, IL19+IGFL1+ keratinocyte subpopulations increase in lesions, which may disrupt the skin barrier, connect and magnify Th2 and Th17 inflammatory responses, and mediate skin pruritus [3]. DNA damage enhances 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 hepatic steatosis, fibrosis, and hepatocellular cancer, overexpression of A1CF leads to increased Il19 expression, along with genes related to oxidative stress, extracellular matrix organization, and proliferation [5]. Also, polymorphisms in the IL19 gene (rs2243191) are associated with the failure to achieve optimal CD4 T-cell restoration in HIV-infected patients on cART [8], and the IL19 SNP rs2243188 is related to the pathogenesis of systemic lupus erythematosus [6]. In chronic rhinosinusitis, Clusters 1 and 2 show non-type 2 signatures with relatively high IL-19 levels [7].

In summary, Il19 is an important cytokine in the IL-10 family with diverse functions. Through studies involving different disease models, it has been shown to play roles in various disease processes such as cancer metastasis, skin inflammation, DNA-damage response, liver diseases, and immunological disorders. These findings contribute to a better understanding of the underlying mechanisms of these diseases and may potentially lead to the development of novel therapeutic strategies targeting Il19.

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/

5. Blanc, Valerie, Riordan, Jesse D, Soleymanjahi, Saeed, Roberts, Lewis R, Davidson, Nicholas O. . Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer. In The Journal of clinical investigation, 131, . doi:10.1172/JCI138699. https://pubmed.ncbi.nlm.nih.gov/33445170/

6. Wang, Weijie, Wang, Xinchang, Yang, Kepeng, Fan, Yongsheng. . Association of BCL2 polymorphisms and the IL19 single nucleotide polymorphism rs2243188 with systemic lupus erythematosus. In The Journal of international medical research, 49, 3000605211019187. doi:10.1177/03000605211019187. https://pubmed.ncbi.nlm.nih.gov/34044633/

7. Wang, Xiangdong, Sima, Yutong, Zhao, Yan, Zhang, Luo, Bachert, Claus. 2022. Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors. In The Journal of allergy and clinical immunology, 151, 458-468. doi:10.1016/j.jaci.2022.10.010. https://pubmed.ncbi.nlm.nih.gov/36272582/

8. García, Marcial, Jiménez-Sousa, María A, Blanco, Julià, Benito, José M, Rallón, Norma. 2019. CD4 recovery is associated with genetic variation in IFNγ and IL19 genes. In Antiviral research, 170, 104577. doi:10.1016/j.antiviral.2019.104577. https://pubmed.ncbi.nlm.nih.gov/31386862/

9. Fujimoto, Yasuyuki, Kuramoto, Nobuyuki, Yoneyama, Masanori, Azuma, Yasu-Taka. . Interleukin-19 as an Immunoregulatory Cytokine. In Current molecular pharmacology, 14, 191-199. doi:10.2174/1874467213666200424151528. https://pubmed.ncbi.nlm.nih.gov/32329704/