Role of Th22 Cells in Human Viral Diseases

Abstract

Naive CD4+ T cells can differentiate into different cell subsets after receiving antigen stimulation, which secrete corresponding characteristic cytokines and thereby exert biological effects in various diseases. Th22 cells, a novel subset of CD4+ T cells, are different from Th1, Th2, Th17, and Treg cell subsets, which have been discovered in recent years. They can express CCR4, CCR6, and CCR10 molecules and secrete IL-22, IL-13, and TNF-α. They are not able to secrete IL-17, IL-4, and interferon-γ (IFN-γ). IL-22 is considered as a major effector molecule of Th22 cells whose functions and mechanisms of regulating cell differentiation have been constantly improved. In this review, we provide an overview of the origin, differentiation of Th22 cells. Moreover, we also describe the interrelationships between Th22 cells and Th17, Th1, and Th2 cells. Additionally, the role of Th22 cells were discussed in human diseases with virus infection, which will provide novel insight for the prevention and treatment of viral infection in human.

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

“…The increased Th17 proportions and IL-22 were observed in cases with headache, hyperinflammation, respiratory system dysfunction, and ARDS ( 163 , 197 ). Other studies indicated that IL-22 levels are negatively correlated with the Th22 levels ( 188 , 198 ). Functional assays revealed that both peripheral blood mononuclear cells (PBMCs) and a human bronchial epithelial cell line (16HBE) can produce IL-22 ( 188 ).…”

“…Other studies indicated that IL-22 levels are negatively correlated with the Th22 levels ( 188 , 198 ). Functional assays revealed that both peripheral blood mononuclear cells (PBMCs) and a human bronchial epithelial cell line (16HBE) can produce IL-22 ( 188 ). This suggests that IL-22 could be expressed differently in peripheral blood and tissues.…”

“…IL-22 belongs to the IL-10 cytokine family and is produced by γδ T cells, Th1 cells, Th17 cells, Th22 cells, NKT cells, and group 3 innate lymphoid cells (ILC3) ( 186 – 188 ). In general, IL-22 is a pro-and anti-inflammatory cytokine involved in tissue inflammation, immunosurveillance, tissue repair, and homeostasis through the IL-22R activation pathway ( 186 , 189 – 195 ).…”

The Role of T Helper 22 Cells in Dermatological Disorders

“…Although IL-22 was primarily discovered that IL-22 was produced by Th1 and natural killer (NK) cells ( 25 ), IL-22 was usually viewed as a Th17 cytokine ( 26 , 27 ) until the identification of Th22 cells ( 8 – 11 ). They were discovered as a new subset that only secreted IL-22, and barely produced IFN-γ, IL-4, or IL-17 ( 15 , 20 ). Duhen estimated that about a half of IL-22 producing CD4+ memory T cells from healthy human peripheral blood secreted only IL-22, whereas around 30% and 13% separately co-expressed IFN-γ and IL-17, separately, with nearly 6% producing all three ( 9 ).…”

Levels of Pathogenic Th17 and Th22 Cells in Patients with Rheumatoid Arthritis

“…Type 22 T helper (Th22) cells are characterized by synthesis of IL-22 (and also IL-13 and TNF- α ) but not IL-17 or IFN- γ [ 27 ]. These lymphocytes, in addition to their role in host defense against different infectious agents and homeostasis, may also exert a proinflammatory effect, participating in the pathogenesis of different immune-mediated conditions such as psoriasis, asthma, inflammatory bowel disease, and systemic sclerosis as well as in viral infections [ 27 , 28 ]. In addition, Th22 and IL-22 seem to have a relevant role in the pathogenesis of RA [ 29 , 30 ].…”