IL-10-Producing B Cells Regulate T Helper Cell Immune Responses during 1,3-β-Glucan-Induced Lung Inflammation

Abstract

With the rapid development of industry and farm, fungi contamination widely exists in occupational environment. Inhalation of fungi-contaminated organic dust results in hypersensitivity pneumonitis. 1,3-β-Glucan is a major cell wall component of fungus and is considered as a biomarker of fungi exposure. Current studies showed that 1,3-β-glucan exposure induced lung inflammation, which involved uncontrolled T helper (Th) cell immune responses, such as Th1, Th2, Th17, and regulatory T cell (Treg). A recently identified IL-10-producing B cells (B10) was reported in regulating immune homeostasis. However, its regulatory role in hypersensitivity pneumonitis is still subject to debate. In our study, we comprehensively investigated the role of B10 and the relationship between B10 and Treg in 1,3-β-glucan-induced lung inflammation. Mice with insufficient B10 exhibited more inflammatory cells accumulation and severer pathological inflammatory changes. Insufficient B10 led to increasing Th1, Th2, and Th17 responses and restricted Treg function. Depletion of Treg before the onset of inflammation could suppress B10. Whereas, Treg depletion only at the late stage of inflammation failed to affect B10. Our study demonstrated that insufficient B10 aggravated the lung inflammation mediated by dynamic shifts in Th immune responses after 1,3-β-glucan exposure. The regulatory function of B10 on Th immune responses might be associated with Treg and IL-10. Treg could only interact with B10 at an early stage.

Regulatory T‐cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide‐induced acute respiratory distress syndrome

“…31 Tregs are generally viewed as a suppressor of Th1 immune responses in various inflammatory diseases. 32,33 However, our finding contradicts the result acquired by Liu et al 20 Differences in the genetic background or the microbiome in the animal may lead to these divergent results; moreover, the discrepant results may also be related to Th1 lymphocyte plasticity. 34,35 Although we observe a decrease in Th1 immune responses following LPS-induced pulmonary damage in Treg-depleted mice, we could not exclude the possibility that the kinetics of their elevation presence in the lungs when the observed time points were prolonged.…”

“…Tregs are generally viewed as a suppressor of Th1 immune responses in various inflammatory diseases . However, our finding contradicts the result acquired by Liu et al . Differences in the genetic background or the microbiome in the animal may lead to these divergent results; moreover, the discrepant results may also be related to Th1 lymphocyte plasticity .…”

“…Previous studies on Treg depletion used Foxp3 DTR mice and intraperitoneal administration of diphtheria toxin or anti‐CD25 neutralization. As CD25 mAb (PC61 mAb) has been confirmed to deplete Foxp3 + Tregs and PC61 has been shown to cause a significant reduction in Foxp3 + Tregs by phagocytes via Ab‐dependent cellular cytotoxicity . In our study, we employed the widely used and easily approachable strategy of PC61 anti‐CD25 mAb treatment to deplete CD4 + FOXP3 + Tregs prior to LPS administration in mice.…”

Associations of Pulmonary Fibrosis with Peripheral Blood Th1/Th2 Cell Imbalance and EBF3 Gene Methylation in Uygur Pigeon Breeder’s Lung Patients

“…Th1 is inhibited by B cells [9], and EBF3 is an essential factor for B cell maturation [3]. Nonetheless, the role of B cells in Th1/Th2 imbalance, i.e., the change from Th1 dominance to Th2 dominance, in PBL remains unclear.…”

IL-10 producing B cells regulated 1,3-β-glucan induced Th responses in coordinated with Treg

“…In order to clarify the regulative mechanism of 1, 3-β-glucan induced IL-10-producing B cells on Teff and Treg respectively, the comprehensive experiments in vitro were carried out. Anti-CD22 mAb was used to restrict the induction of IL-10-producing B cells as previous [23][24][25]. Teff(CD4 + CD25 -), Treg(CD4 + CD25 + ), macrophages and B cells(CD19 + ) were isolated from different group mice.…”