Tlr5, Toll-like receptor 5, is a key innate immune receptor. It recognizes bacterial flagellin and is widely expressed on many cells, including dendritic cells. TLR5 activation can initiate immune-related signaling pathways, modulating immune responses, which is of great biological importance in host-pathogen interactions and immune regulation [2,3,4,5]. Genetic models, such as gene-knockout (KO) mouse models, have been crucial for studying its functions.

In Tlr5-deficient (Tlr5-/-) mice, several key findings have emerged. In a model of Crohn's disease, depletion of TLR5 attenuated the protective effect of Roseburia intestinalis on experimental colitis, suggesting TLR5 is essential for R. intestinalis-mediated increase in anti-inflammatory Tregs differentiation [1]. In an autoimmune diabetes-susceptible model, TLR5-deficiency led to reduced CD11c + DC development in utero, biased DC populations, hyper-secretion of cytokines, and increased diabetogenic CD4 + T cell responses in older mice [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 [3]. In MRL/lpr mice (a lupus-like disease model), Tlr5 deficiency exacerbated lupus-like disease, with increased proteinuria, glomerular IgG and C3 deposition, and renal infiltration of Th17 and activated cDC1 cells [6].

In conclusion, Tlr5 is vital in modulating immune responses and plays significant roles in multiple disease conditions. Studies using Tlr5 KO mouse models have provided valuable insights into its functions in diseases like Crohn's disease, autoimmune diabetes, asthma, and lupus-like diseases, highlighting its potential as a therapeutic target.

References:

1. Shen, Zhaohua, Luo, Weiwei, Tan, Bei, Xu, Jiahao, Wang, Xiaoyan. 2022. Roseburia intestinalis stimulates TLR5-dependent intestinal immunity against Crohn's disease. In EBioMedicine, 85, 104285. doi:10.1016/j.ebiom.2022.104285. https://pubmed.ncbi.nlm.nih.gov/36182776/

2. Pearson, James Alexander, Hu, Youjia, Peng, Jian, Wong, F Susan, Wen, Li. 2024. TLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model. In Frontiers in immunology, 15, 1333967. doi:10.3389/fimmu.2024.1333967. https://pubmed.ncbi.nlm.nih.gov/38482010/

3. Whitehead, G S, Hussain, S, Fannin, R, Cook, D N, Garantziotis, S. 2020. TLR5 Activation Exacerbates Airway Inflammation in Asthma. In Lung, 198, 289-298. doi:10.1007/s00408-020-00337-2. https://pubmed.ncbi.nlm.nih.gov/32060608/

4. Pachathundikandi, Suneesh Kumar, Tegtmeyer, Nicole, Arnold, Isabelle Catherine, Müller, Anne, Backert, Steffen. 2019. T4SS-dependent TLR5 activation by Helicobacter pylori infection. In Nature communications, 10, 5717. doi:10.1038/s41467-019-13506-6. https://pubmed.ncbi.nlm.nih.gov/31844047/

5. Song, Wan Seok, Kim, Jee-Hyeon, Choi, Chi-Min, Lee, Woo-Jong, Yoon, Sung-Il. 2018. TLR5 binding and activation by KMRC011, a flagellin-derived radiation countermeasure. In Biochemical and biophysical research communications, 508, 570-575. doi:10.1016/j.bbrc.2018.11.080. https://pubmed.ncbi.nlm.nih.gov/30509486/

6. Alajoleen, Razan M, Oakland, David N, Estaleen, Rana, Reilly, Christopher M, Luo, Xin M. 2024. Tlr5 deficiency exacerbates lupus-like disease in the MRL/lpr mouse model. In Frontiers in immunology, 15, 1359534. doi:10.3389/fimmu.2024.1359534. https://pubmed.ncbi.nlm.nih.gov/38352866/