Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity

Abstract

CD4+T helper (Th) cells are important mediators of immune responses in asthma and cancer. When counteracted by different classes of pathogens, naïve CD4+T cells undergo programmed differentiation into distinct types of Th cells. Th cells orchestrate antigen-specific immune responses upon their clonal T-cell receptor (TCR) interaction with the appropriate peptide antigen presented on MHC class II molecules expressed by antigen-presenting cells (APCs). T helper 9 (Th9) cells and regulatory T (Treg) cells and their corresponding cytokines have critical roles in tumor and allergic immunity. In the context of asthma and cancer, the dynamic internal microenvironment, along with chronic inflammatory stimuli, influences development, differentiation, and function of Th9 cells and Treg cells. Furthermore, the dysregulation of the balance between Th9 cells and Treg cells might trigger aberrant immune responses, resulting in development and exacerbation of asthma and cancer. In this review, the development, differentiation, and function of Th9 cells and Treg cells, which are synergistically regulated by various factors including cytokine signals, transcriptional factors (TFs), costimulatory signals, microenvironment cues, metabolic pathways, and different signal pathways, will be discussed. In addition, we focus on the recent progress that has helped to achieve a better understanding of the roles of Th9 cells and Treg cells in allergic airway inflammation and tumor immunity. We also discuss how various factors moderate their responses in asthma and cancer. Finally, we summarize the recent findings regarding potential mechanisms for regulating the balance between Th9 and Treg cells in asthma and cancer. These advances provide opportunities for novel therapeutic strategies that are aimed at reestablishing the balance of these cells in the diseases.

Diagnostic Value, Prognostic Value, and Immune Infiltration of LOX Family Members in Liver Cancer: Bioinformatic Analysis

“…The MHCs, HLA-DOA, HLA-DPA1, and HLA-DPB1, positively associated with LOXL3 all belongs to MHC Class II molecules (104). MHC class II molecules were found to be expressed by antigen-presenting cells, including antigenpresenting cancer-associated fibroblasts (apCAFs) (105,106). Therefore, these positive association of the MHC Class II molecules might be indirect evidence of apCAFs in HCC, and drugs targeted on these apCAFs might have potential therapeutic values and future studies are needed for further clarification.…”

Differences in Inflammatory Cytokine Profile in Obesity-Associated Asthma: Effects of Weight Loss

“…On the one hand, IL-9 has been shown to promote Th17 differentiation and production of IL-17 and IL-6 [103]; in contrast, it has also been shown that IL-9 enhances the suppressive function of Treg [104]. Asthma patients have increased numbers of Th9 cells in peripheral blood mononuclear cells (PBMCs) and increased IL-9 levels in both serum and bronchoalveolar lavage fluid (BALF) [105][106][107][108][109]. Th9 cells and IL-9 promote accumulation and activation of T cells, ILC2s, mast cells, and eosinophils and increase levels of IL-5, IL-13, and IgE in animal asthma models [110].…”

Regulatory T Cells, a Viable Target Against Airway Allergic Inflammatory Responses in Asthma

“…Moreover, Th9 cells employ multiple mechanisms to orchestrate allergic inflammation, and particularly, their interaction with diverse cell types including mast cells, ILCs, and DCs, to promote coordinated regulation of allergic airway inflammation (31,32). Other than secretion of their signature cytokine IL-9, Th9 cells from mice and humans also secret other cytokines such as IL-10, IL-17, IL-21, and IL-22, to facilitate immune responses in the setting of allergic asthma (33,34). Furthermore, studies on atopic dermatitis demonstrated feasible evidence supporting that the expansion of Th2/Tc2 and Th22/Tc22 may also exert an important role in allergic inflammation (14,35).…”