Itk, also known as IL-2-inducible T-cell kinase, is a non-receptor tyrosine kinase of the Tec family. It plays a crucial role in T-cell receptor signaling pathways, regulating processes such as phospholipase C-gamma1 activation, actin polymerization, and T-cell proliferation and differentiation [3,4,5]. Itk is also involved in the secretion of various pro-inflammatory cytokines like IL-2, IL-4, IL-5, IL-10, and IL-13, and in the development of effector T-cells, thus being of great biological importance in immune responses [4,5]. Genetic models, such as gene knockout (KO) mouse models, have been instrumental in studying Itk.

In Itk-deficient mice, CD4+ T cells showed a bias against Th2 differentiation and an inability to produce Th2 cytokines in a recall response, indicating Itk's role in Th2 cell development [3]. In a collagen-induced arthritis (CIA) model, an Itk inhibitor alleviated the disease, reduced antigen-specific antibody production, and rebalanced Th17 and regulatory T (Treg) cells, suggesting Itk's importance in rheumatoid arthritis development [1]. In T-cell lymphoma studies, the development of a potent Itk degrader, BSJ-05-037, blocked NF-kB/GATA-3 signaling and increased the sensitivity of lymphoma cells to chemotherapy, highlighting Itk's role in T-cell lymphomas [2].

In conclusion, Itk is essential for T-cell signaling, T-cell-mediated immune responses, and the secretion of multiple cytokines. KO mouse models have revealed its significance in diseases such as rheumatoid arthritis and T-cell lymphomas. Understanding Itk's functions through these models provides insights into the pathogenesis of these diseases and potential therapeutic strategies targeting Itk [1,2,3].