Tlr5, Toll-like receptor 5, is a key innate immune receptor that recognizes bacterial flagellin. It activates downstream signaling pathways, playing a crucial role in the body's immune response against bacterial infections. Genetic models, such as knockout (KO) mice, have been instrumental in studying its functions [2,3,5,6].

In a TNBS-induced colitis mouse model, R. intestinalis was found to inhibit the development of Crohn's disease by increasing anti-inflammatory Tregs differentiation through Tlr5-mediated TSLP production in intestinal epithelial cells. Depletion of Tlr5 attenuated the protective effect of R. intestinalis on experimental colitis [1].

In an autoimmune diabetes-susceptible NOD mouse model, Tlr5-deficiency led to reduced CD11c+ DC development in utero, biased DC populations, and enhanced diabetogenic CD4+ T cell responses, with older Tlr5-deficient mice having a greater risk of developing spontaneous T1D [2].

In a murine model of allergic asthma, activation of Tlr5 by flagellin exacerbated airway inflammation, and a dominant-negative polymorphism in Tlr5 was associated with decreased asthma symptoms in patients [3].

In TNBC cell line 4T1 mouse models, down-regulation of Tlr5 increased tumor invasiveness and EMT expression [4].

In mice, Tlr5 deletion led to a smaller placental labyrinthine zone and lower embryo weight [5].

In MRL/lpr mice with global Tlr5 deletion, lupus-like disease was exacerbated, with increased proteinuria, glomerular IgG and C3 deposition, and renal infiltration of Th17 and activated cDC1 cells [6].

In conclusion, Tlr5 is essential for innate immune responses and is involved in multiple biological processes. KO mouse models have revealed its roles in diseases like Crohn's disease, type 1 diabetes, asthma, triple-negative breast cancer, placental development, and lupus-like disease, providing valuable insights into disease mechanisms and potential therapeutic targets.