Innate lymphoid cells (ILC) are lymphocytes that lack an antigen-specific receptor and are preferentially localized in non-lymphoid tissues, such as mucosal barriers. In these locations ILC respond to tissue perturbations by producing factors that promote tissue repair and improve barrier integrity. We show that mice lacking the Tec kinase ITK have impaired intestinal tissue integrity, and a reduced ability to restore homeostasis after tissue damage. This defect is associated with a substantial loss of Type 2 ILC (ILC2) in the intestinal lamina propria. Adoptive transfer of bone marrow ILC2 precursors confirms a cell-intrinsic role for ITK. Intestinal ILC2 numbers in Itk mice are restored by the administration of IL-2 complexes, also leading to improved intestinal tissue damage repair. Reduced Bcl-2 expression in intestinal Itk ILC2 is also restored to WT levels after IL-2 complex treatment, indicating a tissue-specific role for ITK in ILC2 survival in the intestine.
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http://dx.doi.org/10.1038/s41467-019-08699-9 | DOI Listing |
Arch Dermatol Res
January 2025
Division of Gastroenterology and Hepatology, 200 1st Street SW, Rochester, MN, 55905, USA.
Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
Center for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Taizhou Institute of Zhejiang University, Zhejiang University, Taizhou 318000, China. Electronic address:
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by recurrent eczematous lesions and severe itching, for which clinical treatments are limited. Selectively inhibiting Janus Kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinases is proposed as a promising strategy to treat AD with possible reduced side effects and enhanced efficacy. In this study, we developed a dual JAK3/TEC family kinase inhibitor ZZB, which demonstrated potent inhibitory activity with IC values of 0.
View Article and Find Full Text PDFCell Mol Life Sci
August 2024
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, Wroclaw, 50-383, Poland.
BMC Genomics
July 2024
State Key Laboratory of Tree Genetics and Breeding, College of Life Sciences, Nanjing Forestry University, Nanjing, 210037, China.
Background: Liriodendron chinense is susceptible to extinction due to the increasing severity of abiotic stresses resulting from global climate change, consequently impacting its growth, development, and geographic distribution. However, the L. chinense remains pivotal in both socio-economic and ecological realms.
View Article and Find Full Text PDFArch Dermatol Res
July 2024
Department of Dermatology and Venereology, Hair Medical Research Center, Beijing Jishuitan Hospital, Capital Medical University, No. 31 of Xinjiekou East Street, Xicheng District, Beijing, 100035, China.
The TEC (tyrosine kinase expressed in hepatocellular carcinoma) family kinases, an important class of protein kinases, play key roles in cell signaling and immune regulation. In this review, the association between the pathogenesis of alopecia areata and the structure and regulatory mechanisms of TEC family kinases in normal physiological processes, is explored. Furthermore, the potential clinical applications of TEC kinases and their inhibitors are highlighted by summarizing current insights into their mechanisms of action, clinical applications, and recent advancements in TEC kinase inhibitor research.
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