Il1f10, also known as interleukin 1 family member 10, encodes interleukin-38, a cytokine belonging to the IL-1 family. IL-38 is constitutively expressed in epithelia, especially in epidermal keratinocytes, and its expression is closely related to keratinocyte differentiation [2]. It is involved in multiple biological processes, including inflammation regulation, and may play a role in various disease-related pathways such as those related to gout, atopic dermatitis, and lung function [1,3,4].

In atopic dermatitis, IL-38 is mainly secreted by epidermal keratinocytes. Keratinocyte-specific knockout mice (K14Cre/+-IL-38f/f) showed less susceptibility to cutaneous inflammation of AD, suggesting that IL-38 may aggravate AD by promoting the migration of Langerhans cells [3]. In colitis, IL-38-deficient mice subjected to dextran sulfate sodium (DSS) showed greater disease severity, indicating that endogenous IL-38 acts as an anti-inflammatory cytokine to reduce DSS colitis severity [5].

In conclusion, Il1f10-encoded IL-38 has diverse functions in the body, especially in inflammation-related processes. Studies using gene knockout mouse models have revealed its roles in diseases like atopic dermatitis and colitis, highlighting its potential as a therapeutic target for these inflammatory conditions.

References:

1. Gaal, Orsolya I, Leask, Megan, Nica, Valentin, Crișan, Tania O, Joosten, Leo A B. 2024. Gout-associated SNP at the IL1RN-IL1F10 region is associated with altered cytokine production in PBMCs of patients with gout and controls. In Arthritis research & therapy, 26, 205. doi:10.1186/s13075-024-03436-0. https://pubmed.ncbi.nlm.nih.gov/39568029/

2. Talabot-Ayer, Dominique, Diaz-Barreiro, Alejandro, Modarressi, Ali, Palmer, Gaby. 2022. Epigenetic remodeling of downstream enhancer regions is linked to selective expression of the IL1F10 gene in differentiated human keratinocytes. In Gene, 842, 146800. doi:10.1016/j.gene.2022.146800. https://pubmed.ncbi.nlm.nih.gov/35961432/

3. Yue, Chengcheng, Hu, Yawen, Yu, Jiadong, Cui, Kaijun, Li, Jiong. 2024. IL-38 Aggravates Atopic Dermatitis via Facilitating Migration of Langerhans cells. In International journal of biological sciences, 20, 3094-3112. doi:10.7150/ijbs.93843. https://pubmed.ncbi.nlm.nih.gov/38904012/

4. Kim, Hyun-Jin, Seo, Yong-Seok, Sung, Joohon, Kim, Jong-Il, Park, Jin-Ho. 2019. A genome-wide by PM10 interaction study identifies novel loci for lung function near BICD1 and IL1RN-IL1F10 genes in Korean adults. In Chemosphere, 245, 125581. doi:10.1016/j.chemosphere.2019.125581. https://pubmed.ncbi.nlm.nih.gov/31846791/

5. de Graaf, Dennis M, Wang, Ruth X, Amo-Aparicio, Jesús, Joosten, Leo A B, Dinarello, Charles A. 2022. IL-38 Gene Deletion Worsens Murine Colitis. In Frontiers in immunology, 13, 840719. doi:10.3389/fimmu.2022.840719. https://pubmed.ncbi.nlm.nih.gov/35693797/