The Roles of Immune Cells in the Pathogenesis of Fibrosis.

Tissue injury and inflammatory response trigger the development of fibrosis in various diseases. It has been recognized that both innate and adaptive immune cells are important players with multifaceted functions in fibrogenesis. The activated immune cells produce various cytokines, modulate the differentiation and functions of myofibroblasts via diverse molecular mechanisms, and regulate fibrotic development. The immune cells exhibit differential functions during different stages of fibrotic diseases. In this review, we summarized recent advances in understanding the roles of immune cells in regulating fibrotic development and immune-based therapies in different disorders and discuss the underlying molecular mechanisms with a focus on mTOR and JAK-STAT signaling pathways.

Interleukin-6 blocking therapy for COVID-19: From immune pathogenesis to clinical outcomes.

As a newly emerged infectious disease, the coronavirus disease 2019 (COVID-19) has caused millions of deaths, resulting in a global health challenge. Currently, several vaccines have been approved with significant benefits against disease transmission. However, effective therapies are still needed for the clinical management of infected COVID-19 patients. Available evidence has indicated elevated levels of proinflammatory cytokines, including interleukin-6 (IL-6), in COVID-19 patients, with cytokine storm involving excessive cytokine release being observed in some severe cases. Several clinical studies have shown the promising effects of IL-6-blocking strategy in treating severe COVID-19 patients, but some observational studies have reported that IL-6-blocking therapy has no effects in preventing disease progression or death among COVID-19 patients. Herein, we review recent findings on the immunopathogenesis of COVID-19, with specific emphasis on the proinflammatory function of IL-6 and discuss the therapeutic potential of IL-6-blocking therapy for the treatment of COVID-19 patients, especially those with rheumatic diseases.

Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious infectious disease that has led to a global pandemic with high morbidity and mortality. High-affinity neutralizing antibody is important for controlling infection, which is closely regulated by follicular helper T (Tfh) cells. Tfh cells play a central role in promoting germinal center reactions and driving cognate B cell differentiation for antibody secretion. Available studies indicate a close relationship between virus-specific Tfh cell-mediated immunity and SARS-CoV-2 infection progression. Although several lines of evidence have suggested that Tfh cells contribute to the control of SARS-CoV-2 infection by eliciting neutralizing antibody productions, further studies are needed to elucidate Tfh-mediated effector mechanisms in anti-SARS-CoV-2 immunity. Here, we summarize the functional features and roles of virus-specific Tfh cells in the immunopathogenesis of SARS-CoV-2 infection and in COVID-19 vaccines, and highlight the potential of targeting Tfh cells as therapeutic strategy against SARS-CoV-2 infection.

The immune dysregulations in COVID-19: Implications for the management of rheumatic diseases.

The pandemic of COVID-19 has caused global social impact and high health risk. Clinical observations have suggested that elevated levels of inflammatory mediators are associated with disease severities in COVID-19 patients, in which the immunological profiles indicate the hyperactivation of innate immune cells and dysregulated adaptive immune responses. The increasing prevalence and disease progression of COVID-19 has emerged as a pressing challenge for the management of rheumatic patients with immune dysregulations. Here we review the immune dysregulations in COVID-19 and discuss the management of COVID-19 patients with rheumatic diseases.