COVID-19 immunopathology with emphasis on Th17 response and cell-based immunomodulation therapy: Potential targets and challenges

The role of the immune system against coronavirus disease 2019 (COVID-19) is unknown in many aspects, and the protective or pathologic mechanisms of the immune response are poorly understood. Pro-inflammatory cytokine release and a consequent cytokine storm can lead to acute respiratory distress syndrome (ARDS) and result in multi-organ failure. There are many T cell subsets during anti-viral immunity. The Th17-associated response, as a pro-inflammatory pathway, and its consequent outcomes in many autoimmune disorders play a fundamental role in progression of systemic hyper-inflammation during COVID-19. Therapeutic strategies based on immunomodulation therapy could be helpful for targeting hyper-inflammatory immune responses in COVID-19, especially Th17-related inflammation and hyper-cytokinemia. Cell-based immunotherapeutic approaches including mesenchymal stem cells (MSCs), tolerogenic dendritic cells (tolDCs) and regulatory T cells (Tregs) seem to be promising strategies as orchestrators of the immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we highlight Th17-related immunopathology of SARS-CoV-2 infection and discuss cell-based immunomodulatory strategies and their mechanisms for regulation of the hyper-inflammation during COVID-19.