Influenza is a major respiratory viral disease caused by infections from the influenza A virus (IAV) that persists across various seasonal outbreaks globally each year. Host immune response is a key factor determining disease severity of influenza infection, presenting an attractive target for the development of novel therapies for treatments. Among the multiple signal transduction pathways regulating the host immune activation and function in response to IAV infections, the mitogen-activated protein kinase (MAPK) pathways are important signalling axes, downstream of various pattern recognition receptors (PRRs), activated by IAVs that regulate various cellular processes in immune cells of both innate and adaptive immunity. Moreover, aberrant MAPK activation underpins overexuberant production of inflammatory mediators, promoting the development of the “cytokine storm”, a characteristic of severe respiratory viral diseases. Therefore, elucidation of the regulatory roles of MAPK in immune responses against IAVs is not only essential for understanding the pathogenesis of severe influenza, but also critical for developing MAPK-dependent therapies for treatment of respiratory viral diseases. In this review, we will summarise the current understanding of MAPK functions in both innate and adaptive immune response against IAVs and discuss their contributions towards the cytokine storm caused by highly pathogenic influenza viruses.

Protein tyrosine phosphatases (PTPs) act as key regulators in various cellular processes such as proliferation, differentiation, and migration. Our previous research demonstrated that non-receptor-typed PTP21 (PTPN21), a member of the PTP family, played a critical role in the proliferation, cell cycle, and chemosensitivity of acute lymphoblastic leukemia cells. However, the role of PTPN21 in the bone marrow microenvironment has not yet been elucidated. In the study, we explored the effects of PTPN21 on human bone marrow-derived mesenchymal stem cells (BM-MSCs) via lentiviral-mediated overexpression and knock-down of PTPN21 in vitro. Overexpressing PTPN21 in BM-MSCs inhibited the proliferation through arresting cell cycle at the G₀phase but rendered them a higher osteogenic and adipogenic differentiation potential. In addition, overexpressing PTPN21 in BM-MSCs increased their senescence levels through upregulation of P21 and P53 and dramatically changed the levels of crosstalk with their typical target cells including immunocytes, tumor cells, and vascular endothelial cells. BM-MSCs overexpressing PTPN21 had an impaired immunosuppressive function and an increased capacity of recruiting tumor cells and vascular endothelial cells in a chemotaxis transwell coculture system. Collectively, our data suggested that PTPN21 acted as a pleiotropic factor in modulating the function of human BM-MSCs.