Emerging Effects of IL-33 on COVID-19.

Since the start of COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 6 million people have lost their lives worldwide directly or indirectly. Despite intensified efforts to clarify the immunopathology of COVID-19, the key factors and processes that trigger an inflammatory storm and lead to severe clinical outcomes in patients remain unclear. As an inflammatory storm factor, IL-33 is an alarmin cytokine, which plays an important role in cell damage or infection. Recent studies have shown that serum IL-33 is upregulated in COVID-19 patients and is strongly associated with poor outcomes. Increased IL-33 levels in severe infections may result from an inflammatory storm caused by strong interactions between activated immune cells. However, the effects of IL-33 in COVID-19 and the underlying mechanisms remain to be fully elucidated. In this review, we systematically discuss the biological properties of IL-33 under pathophysiological conditions and its regulation of immune cells, including neutrophils, innate lymphocytes (ILCs), dendritic cells, macrophages, CD4+ T cells, Th17/Treg cells, and CD8+ T cells, in COVID-19 phagocytosis. The aim of this review is to explore the potential value of the IL-33/immune cell pathway as a new target for early diagnosis, monitoring of severe cases, and clinical treatment of COVID-19.

Exploring the Role of Innate Lymphocytes in the Immune System of Bats and Virus-Host Interactions.

Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic viruses, they rarely display signs of disease. Recent insights suggest that bats have a more balanced host defense and tolerance system to viral infections that may be linked to the evolutionary adaptation to powered flight. Therefore, a deeper understanding of bat immune system may provide intervention strategies to prevent zoonotic disease transmission and to identify new therapeutic targets. Similar to other eutherian mammals, bats have both innate and adaptive immune systems that have evolved to detect and respond to invading pathogens. Bridging these two systems are innate lymphocytes, which are highly abundant within circulation and barrier tissues. These cells share the characteristics of both innate and adaptive immune cells and are poised to mount rapid effector responses. They are ideally suited as the first line of defense against early stages of viral infections. Here, we will focus on the current knowledge of innate lymphocytes in bats, their function, and their potential role in host-pathogen interactions. Moreover, given that studies into bat immune systems are often hindered by a lack of bat-specific research tools, we will discuss strategies that may aid future research in bat immunity, including the potential use of organoid models to delineate the interplay between innate lymphocytes, bat viruses, and host tolerance.

[Mechanism and intervention of mucosal immune regulation based on "lung and large intestine being interior-exteriorly related" theory of traditional Chinese medicine].

The "lung and large intestine being interior-exteriorly related" is one of the classical theories in traditional Chinese medicine, which indicates a close correlation between the lung and large intestine in physiology and pathology, and plays a pivotal role in guiding the treatment of the lung and bowel diseases. Modern medicine has revealed some connections between the lung and large intestine in tissue origin and mucosal immunity, and preliminarily illuminated the material basis and possible regulatory mechanism of the theory. Recently, this theory has been applied to guide the treatment of refractory lung and intestine diseases such as COVID-19 and ulcerative colitis and has obtained reliable efficacy. Existing research results show that the anatomical homogeneity of lung and large intestine promotes the correlation between lung-bowel mucosal immunity, and mucosal immunity and migration and homing of innate lymphocytes are one of the physiological and pathological mechanisms for lung and large intestine to share. Under the guidance of this theory, Chinese medicines with heat-clearing and detoxifying or tonic effects are commonly used in the treatment of the lung and intestinal diseases by regulating lung-bowel mucosal immunity and they can be candidate drugs to treat lung/intestinal diseases simultaneously. However, the existing studies on immune regulation are mainly focused on the expression levels of sIgA and cytokines, as well as the changes in the number of immune cells such as innate lymphocytes and B lymphocytes. While the following aspects need further investigation: the airway/intestinal mucous hypersecretion, the functional changes of pulmonary and intestinal mucosal barrier immune cells, the dynamic process of lung/intestinal mucosal immune interaction, the intervention effect of local pulmonary/intestinal microecology, the correlation and biological basis between the heat-clearing and detoxifying effect and the tonic effect, and its regulation of pulmonary/intestinal mucosal immunity. In this paper, we try to analyze the internal relationship between lung and intestine related diseases from the point of view of the common mucosal immune system of lung and intestine, and summarize the characteristics and rules of traditional Chinese medicine compound and its active ingredients, which have regulatory effect on lung and intestine mucosal immune system, so as to further explain the theoretical connotation of "lung and large intestine being interior-exteriorly related" and provide reference for the research and development of drugs for related diseases.