Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis

Abstract

Type 2 helper T (Th2) cells, a subset of CD4+ T cells, play an important role in the host defense against pathogens and allergens by producing Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, to trigger inflammatory responses. Emerging evidence reveals that Th2 cells also contribute to the repair of injured tissues after inflammatory reactions. However, when the tissue repair process becomes chronic, excessive, or uncontrolled, pathological fibrosis is induced, leading to organ failure and death. Thus, proper control of Th2 cells is needed for complete tissue repair without the induction of fibrosis. Recently, the existence of pathogenic Th2 (Tpath2) cells has been revealed. Tpath2 cells produce large amounts of Th2 cytokines and induce type 2 inflammation when activated by antigen exposure or tissue injury. In recent studies, Tpath2 cells are suggested to play a central role in the induction of type 2 inflammation whereas the role of Tpath2 cells in tissue repair and fibrosis has been less reported in comparison to conventional Th2 cells. In this review, we discuss the roles of conventional Th2 cells and pathogenic Th2 cells in the sequence of tissue inflammation, repair, and fibrosis.

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

“…74 Classically, AD lesions are characterized by an increased expression of Th2 cytokines, which have been implicated in tissue repair. 75 Indeed, cytokine-related genes represent a sizeable group of potential offender genes whose variants have been associated with AD 35,64,76,77 [Table 1]. As a result of inherent barrier defects such as FLG mutations or lipid deficiencies, there is an overproduction of Th2 cytokines (classically IL4, IL13, and IL31) in the skin lesions of predisposed individuals [Figure 1].…”

3D chromatin reprogramming primes human memory T H 2 cells for rapid recall and pathogenic dysfunction

“…We next investigated whether the recall-associated transcriptional and epigenomic signatures we identified could be linked to memory T cell dysfunction in human disease. Asthma is one of the most common chronic inflammatory disorders, with most patients exhibiting excessive pulmonary type 2 inflammation often driven by aberrant memory T H 2 cell activity ( 6 , 7 ). We performed RNA-Seq on resting memory T H 2 cells from peripheral blood samples of healthy controls and patients with asthma with either mild-to-moderate or severe disease (i.e., low or high symptom burden; see Methods and table S1).…”

“…Memory T cells thus provide long-lasting immunological protection, forming the foundation for vaccination strategies ( 4 ). Moreover, pathogenic dysfunction of memory T cells has been implicated in major diseases, including autoimmunity [T H 17 cells ( 5 )] and asthma [T H 2 cells ( 6 , 7 )].…”

Effective-mononuclear cell (E-MNC) therapy alleviates salivary gland damage by suppressing lymphocyte infiltration in Sjögren-like disease

“…As mentioned above, CCR4 + /CCR6 − Th2 cells were also enriched in E-MNCs. Th2 cells are known to produce anti-inflammatory cytokines such as IL-4, IL-10, IL-13, and TGF-β ( Young et al, 2000 ; Wegmann, 2009 ; Iwaszko et al, 2021 ; Kokubo et al, 2022 ). Moreover, galectin3 produced by macrophages plays a major role in the activation of M2 polarization via IL-4 signaling in Th2 cells ( MacKinnon et al, 2008 ; Sperandio et al, 2009 ; Espinosa Gonzalez et al, 2022 ).…”