Socs3, short for suppressor of cytokine signaling 3, is a key negative regulator of cytokine signaling, especially crucial in modulating the JAK-STAT signaling pathway. It plays an essential role in maintaining immune homeostasis, energy metabolism, and cell growth regulation. Genetic models, like KO/CKO mouse models, have been instrumental in understanding its functions [2,4,5].

In KO mouse models, Socs3 deficiency in myeloid cells led to more severe dextran sulfate sodium (DSS)-induced colitis, indicating its role in preventing over-activation of the immune system in inflammatory bowel diseases [3]. Cardiac-specific deletion of Socs3 enhanced cardioprotective signaling pathways, inhibited myocardial apoptosis and fibrosis, and prevented left ventricular remodeling after myocardial infarction [4]. Also, loss of Socs3 in the mouse liver increased the rate of liver regeneration and made hepatocytes prone to neoplastic transformation [1].

In conclusion, Socs3 is vital for regulating cytokine signaling, immune responses, and tissue-specific functions. Studies using KO/CKO mouse models have revealed its significance in diseases such as inflammatory bowel diseases, heart diseases, and liver diseases, providing potential therapeutic targets for these conditions.

References:

1. Khan, Md Gulam Musawwir, Ghosh, Amit, Variya, Bhavesh, Ramanathan, Sheela, Ilangumaran, Subburaj. 2019. Hepatocyte growth control by SOCS1 and SOCS3. In Cytokine, 121, 154733. doi:10.1016/j.cyto.2019.154733. https://pubmed.ncbi.nlm.nih.gov/31154249/

2. Carow, Berit, Rottenberg, Martin E. 2014. SOCS3, a Major Regulator of Infection and Inflammation. In Frontiers in immunology, 5, 58. doi:10.3389/fimmu.2014.00058. https://pubmed.ncbi.nlm.nih.gov/24600449/

3. Zhou, Lianna, Yan, Zhaoqi, Yang, Wei, Benveniste, Etty N, Qin, Hongwei. 2023. Socs3 expression in myeloid cells modulates the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. In Frontiers in immunology, 14, 1163987. doi:10.3389/fimmu.2023.1163987. https://pubmed.ncbi.nlm.nih.gov/37283760/

4. Yasukawa, Hideo, Nagata, Takanobu, Oba, Toyoharu, Imaizumi, Tsutomu. . SOCS3: A novel therapeutic target for cardioprotection. In JAK-STAT, 1, 234-40. doi:10.4161/jkst.22435. https://pubmed.ncbi.nlm.nih.gov/24058778/

5. White, Christine A, Nicola, Nicos A. 2013. SOCS3: An essential physiological inhibitor of signaling by interleukin-6 and G-CSF family cytokines. In JAK-STAT, 2, e25045. doi:10.4161/jkst.25045. https://pubmed.ncbi.nlm.nih.gov/24416642/