Role of the JAK-STAT Pathway in Bovine Mastitis and Milk Production

Simple Summary The cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway has an important role in the regulation of immunity and inflammation. In addition, the signaling of this pathway has been reported to be associated with mammary gland development and milk production. Because of such important functions, the JAK-STAT pathway has been widely targeted in both human and animal diseases as a therapeutic agent. Recently, the JAK2, STATs, and inhibitors of the JAK-STAT pathway, especially cytokine signaling suppressors (SOCSs), have been reported to be associated with milk production and mastitis-resistance phenotypic traits in dairy cattle. Thus, in the current review, we attempt to overview the development of the JAK-STAT pathway role in bovine mastitis and milk production. The cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a sequence of communications between proteins in a cell, and it is associated with various processes such as cell division, apoptosis, mammary gland development, lactation, anti-inflammation, and immunity. The pathway is involved in transferring information from receptors on the cell surface to the cell nucleus, resulting in the regulation of genes through transcription. The Janus kinase 2 (JAK2), signal transducer and activator of transcription A and B (STAT5 A & B), STAT1, and cytokine signaling suppressor 3 (SOCS3) are the key members of the JAK-STAT pathway. Interestingly, prolactin (Prl) also uses the JAK-STAT pathway to regulate milk production traits in dairy cattle. The activation of JAK2 and STATs genes has a critical role in milk production and mastitis resistance. The upregulation of SOCS3 in bovine mammary epithelial cells inhibits the activation of JAK2 and STATs genes, which promotes mastitis development and reduces the lactational performance of dairy cattle. In the current review, we highlight the recent development in the knowledge of JAK-STAT, which will enhance our ability to devise therapeutic strategies for bovine mastitis control. Furthermore, the review also explores the role of the JAK-STAT pathway in the regulation of milk production in dairy cattle.