Map3k8, also known as Cot/Tpl2, is a serine/threonine kinase. It activates the MKK1/2-ERK1/2 MAPK pathway downstream from multiple receptors such as interleukin-1R, tumor necrosis factor-αR, etc. It plays a key role in innate and adaptive immunity, and influences various inflammatory processes and is involved in regulating cell functions [2].

In gene-knockout (KO) mouse models, Map3k8 deficiency led to smaller numbers of certain monocyte subtypes in ApoE-/-mice fed a high-fat diet, with monocytes showing high apoptosis rates and irregular cytokine expression, suggesting its role in atherogenesis [2]. In lipopolysaccharide-induced emergency granulopoiesis, Map3k8-/-mice had decreased production of granulocyte colony-stimulating factor (G-CSF) and impaired neutrophil precursor proliferation, indicating its requirement for this process [3]. In the context of pulmonary fibrosis, Map3k8 mRNA levels were decreased in IPF patients and in a mouse model of pulmonary fibrosis. Ubiquitous or macrophage-specific deletion of Map3k8 exacerbated the disease, showing its role in regulating inflammatory responses and Cox-2-mediated PGE2 production in the lung [1].

In conclusion, Map3k8 is crucial for regulating immune and inflammatory responses. Studies using KO mouse models have revealed its significant contributions in diseases such as atherogenesis, pulmonary fibrosis, and emergency granulopoiesis, providing insights into potential therapeutic strategies targeting Map3k8 in these disease areas.