Dataset Information

Single cell analysis uncovers striking cellular heterogeneity of lung infiltrating Tregs during steroid-responsive vs. steroid-resistant allergic airway inflammation

ABSTRACT: Allergic airway inflammation is a chronic inflammatory condition resulting from uncontrolled immune responses to environmental antigens. While it is well-established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types like eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the exact mechanisms responsible for such pathogenesis remain largely elusive. Foxp3+ regulatory T cells (Treg) is an indispensable immune regulator during chronic inflammation including allergic airway inflammation. Emerging evidence suggests that Tregs infiltrating inflamed tissues exhibit distinct phenotypes dependent on the specific tissue sites and can display significant heterogeneity and tissue residency. Whether diverse allergic inflammatory responses in the lung influences infiltrating Treg heterogeneity or Treg lung residency has not previously been explored. We employed an unbiased single-cell RNAseq approach to study lung-infiltrating Tregs in models of eosinophilic and neutrophilic airway inflammation models, in which Tregs are critical immune regulators of inflammation. We found that lung-infiltrating Tregs are highly heterogeneous and that Tregs displaying lung residency phenotypes are significantly different depending on the types of inflammation. Tregs expression of ST2, a receptor for alarmin cytokine IL-33, was predominantly induced by eosinophilic inflammation and by tissue residency. However, Treg-specific ST2 deficiency did not affect the development of eosinophilic allergic inflammation nor the generation of lung resident Tregs. These results uncover a striking heterogeneity among Tregs infiltrating the lungs during allergic airway inflammation. The results also indicate that varying types of inflammation may give rise to phenotypically distinct lung resident Tregs. Thus, the present study underscores a novel mechanism by which inflammatory environments may shape the composition of infiltrating Tregs, allowing them to regulate inflammatory responses through tissue-adapted mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE243653 | GEO | 2024/06/12

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Memory helper T cells provide long-lasting host defeMemory helper T cells provide long-lasting host defense against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown. We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2hi memory T helper-2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils. Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders. against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown. We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2 hi memory T helper-2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils. Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders.

Dataset Information

Single cell analysis uncovers striking cellular heterogeneity of lung infiltrating Tregs during steroid-responsive vs. steroid-resistant allergic airway inflammation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets