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Reciprocal regulation of Th2 and stroma cells remodels mesenteric adipose tissue in type 2 inflammation

ABSTRACT: Adipose tissue (AT) contains mesenchymal stromal cells (MSC) in stages of commitment to becoming specialized tissue cells, including adipocytes and fibroblasts, and immune cells which support tissue homeostasis. How MSC and immune cells interact during infection is poorly understood. We show that during intestinal helminth infection MSC in mesenteric AT (mAT) become enriched in non-differentiated progenitor cells. This is accompanied by MSC-intrinsic metabolic reprogramming supporting increased secretion of extracellular matrix (ECM), IL-33, and TSLP. In parallel, Th2 resident memory (Th2RM) cells populate the mAT and persist after infection is resolved. These cells express Areg, TGFβ and IL-5, and are necessary to promote infection induced changes within mAT, including MSC reprogramming and tissue eosinophilia. In turn, IL-33 and TSLP from MSC facilitate Th2RM activation and maintenance. Our findings link Th2RM cells to mAT remodeling during intestinal infection, underscoring the reciprocal dependence of stroma and resident immune cells for lasting tissue immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE186160 | GEO | 2022/08/17

REPOSITORIES: GEO

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Intestinal type 2 inflammation reprograms mesenteric adipose tissue and permanently alters its resident immune cell niche [2022_RNA_2]

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2022-10-13 | GSE215137 | GEO

Intestinal type 2 inflammation reprograms mesenteric adipose tissue and permanently alters its resident immune cell niche [single-cell RNA-seq]

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Adventitial stromal cells define group 2 innate lymphoid cell tissue niches

Project description:We identify a subset of IL-33 expressing adventitial stromal cells as local regulators of ILC2s Type 2 lymphocytes promote both physiologic tissue remodeling and allergic pathology, yet their physical tissue niches are poorly described. In this study, we used quantitative imaging together with scRNAseq to define tissue niches of group 2 innate lymphoid cells (ILC2s), critical instigators of type 2 immunity. We identified a dominant adventitial cuff niche around lung bronchi and larger vessels in multiple tissues, where ILC2s localized with subsets of dendritic and regulatory T cells. However, ILC2s were most intimately associated with adventitial stromal cells (ASC), a mesenchymal fibroblast-like subset that expressed Interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP) and supported ILC2s and tissue-resident Th2 cells.

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M2-like dermis resident macrophages regulate type 1 2 circuitries with ILC2s and eosinophils to exacerbate cutaneous leishmaniasis

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Homo sapiens

Project description:Human ILC2 cells stimulated with IL-25, IL-33, or TSLP

| PRJNA194071 | ENA

Human ILC2 cells stimulated with IL-25, IL-33, or TSLP

Project description:ILC2 cells are a newly described cell type whose biology and contribution to disease are poorly understood. ILC2 cells are activated by allergens, viral infection, and/or epithelial damage via IL-33 and IL-25. ILC2 cells require IL-2, IL-7, IL-25 and IL-33 for their survival and expansion. In mice, ILC2s produce multiple mediators primarily associated with type 2 inflammation (IL-13, IL-5, IL-4, IL-6, IL-9, IL-10, GM-CSF, amphiregulin). ILC2 cells may contribute to the pathology of asthma through multiple mediators that include IL-13-independent pathways. Our goal is to compare transcriptional profiles of IL-33- or IL-25-activated ILC2 cells from blood to characterize these cells and to identify marker(s) that can be utilized to detect them in human tissue. ILC2 cells (Lineage negative, CRTH2+, CD161+, CD127+) were purified from human blood of 5 different donors by flow cytometry. The ILC2 yield ranged from 20,000 to 165,000 cells per donor (0.001-0.008% WBC). Purified ILC2s were expanded in vitro in the presence of IL-2, IL-7, IL-33 and IL-25 (each at 50 ng/ml) for 7-10 days. Expanded cells maintained the ILC2 phenotype (Lineage negative, CRTH2+, CD161+, CD127+). The cells were rested for 2 days in the presence of 1 ng/ml IL-2 and IL-7 and then treated in the presence of 1 ng/ml IL-2 and IL-7 with either media control, IL-25 (50 ng/ml), IL-33 (50 ng/ml), and/or TSLP (50 ng/ml) in combination, for 6 or 24 hours. Whole RNA was isolated via the RNeasy kit (Qiagen). Stratagene Universal Human Reference RNA was used as the reference.

2013-12-31 | E-GEOD-45458 | biostudies-arrayexpress

The CD27/CD70 pathway negatively regulates visceral adipose tissue resident Th2 cells and controls metabolic homeostasis

Project description:The adipose tissue homeostasis relies on the interplay between several regulatory lineages, such as ILC2, Th2, Treg, eosinophils and type 2 macrophages. Among them, ILC2 are numerically the dominant source of type 2 cytokines and are considered as major regulators of adiposity. Despite the overlap in immune effector molecules and sensitivity to alarmins (TSLP, IL-33) between ILC2 and resident memory Th2 lymphocytes, the role of the adaptive axis of type-2 immunity remains unclear. We show that mice deficient for CD27, a member of the TNF receptor superfamily, are more resistant to obesity and associated disorders. A comparative analysis of the CD4 compartment of both strains revealed higher numbers of fat resident memory Th2 cells in the adipose tissue of CD27KO mice, which correlated with decreased PD-1-induced apoptosis. Our data point to a non-redundant role for Th2 lymphocytes in obesogenic conditions.

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Project description:Group 2 innate lymphoid cells (ILC2s) reside in multiple tissues including lymphoid organs and barrier surfaces, and secrete type 2 cytokines including interleukin (IL)-5, IL-9 and IL-13. These cells participate in multiple physiological processes including allergic inflammation, tissue repair, metabolic homeostasis and host defense against helminth infections. Recent studies indicate that neuropeptides can play an important role in regulating ILC2 responses, however, the mechanisms that underlie these processes in vivo remain incompletely defined. Here, we identify that activated ILC2s upregulate choline acetyltransferase (ChAT)—the enzyme responsible for the biosynthesis of acetylcholine (ACh)—following infection with the helminth parasite Nippostrongylus brasiliensis or treatment with alarmins or cytokines including IL-25, IL-33 and thymic stromal lymphopoietin (TSLP). ILC2s also express acetylcholine receptors (AChRs), and ACh administration promotes ILC2 cytokine production and elicits expulsion of helminth infection. In accordance with this, ChAT deficiency in ILC2s leads to defective ILC2 responses and impaired immunity against helminth infection. Together, these results reveal a previously unrecognized role of the ChAT-ACh pathway in promoting type 2 innate immunity to helminth infection.

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