Tnf, also known as Tumour Necrosis Factor α, is a classical pro-inflammatory cytokine that plays a significant role in various physiological and pathological processes, including immunity, inflammation, and apoptosis [2,3,4,5]. It is involved in multiple pathways, such as those related to cell-to-cell contact signaling and immune-mediated responses [1]. TNF-α binds to two specific receptors, TNF-R1 and TNF-R2, triggering complex signaling cascades that can lead to both cell death and survival signals [5]. Genetic models, like gene knockout (KO) mouse models, are valuable tools for studying Tnf.

In myocarditis, mice with genetic deletion of Tnf (Tnf+/- and Tnf-/-) showed a reduced incidence of myocarditis upon immunization with α-myosin heavy chain peptide, but susceptible animals had extensive heart inflammation. In the transgenic T cell receptor (TCRM) model, defective TNF-α production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. These findings suggest that TNF-α promotes myocarditis development by activating cardiac endothelial cells, yet protects from exacerbating cardiac inflammation in established disease by inducing activation-induced cell death of heart-reactive effector CD4+ T cells [2].

In conclusion, Tnf is a crucial cytokine involved in inflammation, immunity, and apoptosis. Through KO mouse models in myocarditis studies, it has been revealed that Tnf plays a dual-edged role in heart-related diseases, both promoting and protecting against disease progression. Understanding Tnf's function through such model-based research provides insights into the complex mechanisms of diseases and may guide the development of more targeted therapeutic strategies for heart-related conditions [2].

References:

1. Horiuchi, Takahiko, Mitoma, Hiroki, Harashima, Shin-ichi, Tsukamoto, Hiroshi, Shimoda, Terufumi. 2010. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. In Rheumatology (Oxford, England), 49, 1215-28. doi:10.1093/rheumatology/keq031. https://pubmed.ncbi.nlm.nih.gov/20194223/

2. Rolski, Filip, Tkacz, Karolina, Węglarczyk, Kazimierz, Kania, Gabriela, Błyszczuk, Przemysław. . TNF-α protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart-reactive CD4+ T cells. In Cardiovascular research, 120, 82-94. doi:10.1093/cvr/cvad158. https://pubmed.ncbi.nlm.nih.gov/37879102/

3. Wang, Youlin, Liu, Jing, Wang, Yongchen. 2023. Role of TNF-α-induced m6A RNA methylation in diseases: a comprehensive review. In Frontiers in cell and developmental biology, 11, 1166308. doi:10.3389/fcell.2023.1166308. https://pubmed.ncbi.nlm.nih.gov/37554306/

4. Rolski, Filip, Błyszczuk, Przemysław. 2020. Complexity of TNF-α Signaling in Heart Disease. In Journal of clinical medicine, 9, . doi:10.3390/jcm9103267. https://pubmed.ncbi.nlm.nih.gov/33053859/

5. Ihnatko, R, Kubes, M. . TNF signaling: early events and phosphorylation. In General physiology and biophysics, 26, 159-67. doi:. https://pubmed.ncbi.nlm.nih.gov/18063842/