Tmem176b-flox Mouse

Tmem176b, a member of the membrane spanning 4-domains (MS4) family, is an intracellular cation channel. It functions as a dual immunoregulator, involved in regulating immune responses, such as inhibiting effector immune responses in some situations and promoting immunity by supporting antigen presentation in others. It also has potential roles in regulating type 2 and 3 immunity, modulating DC biology, inflammasome activation, and CD8+ T cell responses [1].

Disruption of Tmem176b contributes to CD8+ T cell-mediated tumor growth inhibition by unleashing inflammasome activation. Lack of Tmem176b enhances the antitumor activity of anti-CTLA-4 antibodies through caspase-1/IL-1β activation. Pharmacologic de-repression of the inflammasome by targeting Tmem176B may enhance the therapeutic efficacy of immune checkpoint blockers [2].

In triple-negative breast cancer, silencing Tmem176b or inhibiting it with a therapeutic antibody impairs cell proliferation, while overexpression increases proliferation. The AKT/mTOR signaling pathway is regulated by Tmem176b expression in breast cancer cells [3].

In lung adenocarcinoma, Tmem176b promotes cellular functions and tumor growth, and regulates EMT via the FGFR1/JNK/Vimentin/Snail signaling cascade [4].

A subpopulation of CD146+ macrophages exerts antitumor activity by partially inhibiting Tmem176B to activate the NLRP3 inflammasome, and treatment with a Tmem176B inhibitor enhances their antitumor activity [5].

In ovarian cancer, Tmem176b inhibits tumor progression by regulating EMT via the Wnt/β-catenin signaling pathway [6].

In non-small cell lung cancer, Tmem176b is one of the differentiation-related genes in tumor-associated macrophages with potential prognostic value [7].

Overexpression of Tmem176B in mice alleviates bleomycin-induced pulmonary fibrosis by inhibiting the TGFβ1-SMAD signaling pathway [8].

In respiratory viral infections, Tmem176B is involved in inflammasome activation, myeloid immune cell development, etc., and has potential prognostic value [9].

In colorectal cancer, the Ala134Thr variant in Tmem176B is a protective factor for prognosis, associated with increased NLRP3 inflammasome activation [10].

In conclusion, Tmem176b plays crucial roles in immune regulation, tumor development, and other biological processes. Gene knockout or conditional knockout mouse models and other functional studies have revealed its functions in various diseases, including cancers, pulmonary fibrosis, and respiratory viral infections. Understanding the role of Tmem176b provides potential therapeutic targets and new insights into disease treatment.