Dataset Information

Single-cell RNA-seq dictionary of in vivo immune responses to cytokines

ABSTRACT: Cytokines mediate cell-cell communication in the immune system and represent important therapeutic targets. While there have been in-depth studies of individual cytokines, we lack a global view of the responses of each major immune cell type to each cytokine. To address this gap we created the Immune Dictionary — a compendium of single-cell transcriptomic profiles of over 17 immune cell types in response to each of 86 cytokines in murine lymph nodes in vivo. A cytokine-centric view of the dictionary revealed that most cytokines induce highly cell-type-specific responses. For example, the inflammatory cytokine IL-1β induced distinct gene programs in almost every cell type. A cell-type-centric view identified both known and previously uncharacterized cytokine-induced polarization states in every immune cell type, such as a polyfunctional state of NK cells induced by IL-18. Based on the dictionary, we developed companion software, Immune Response Enrichment Analysis (IREA), for assessing immune cell polarization and cytokine activities in any transcriptomic data, and applied it to infer cytokine networks in tumors following immune checkpoint blockade therapy. Our dictionary generates new hypotheses for cytokine functions, illuminates pleiotropic effects of cytokines, expands our knowledge of activation states in each immune cell type, and provides a framework to deduce the roles of specific cytokines and cell-cell communication networks in any immune response.

ORGANISM(S): Mus musculus

PROVIDER: GSE202186 | GEO | 2023/07/17

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Inflammation is the natural defensive response of the immune system to an injury or infection and is regulated by small molecule mediators triggering different phases of the inflammatory process. In particular, lipid mediators (LM) and cytokines exhibit crucial regulatory functions in the progression and resolution of inflammation. Macrophages play a central role in this process and can adopt distinct phenotypes with specialized functions depending on their microenvironment: inflammatory M1 macrophages drive inflammation by the release of pro-inflammatory cytokines and LMs, like prostaglandins (PG) and leukotrienes (LT), while resolving M2 macrophages promote inflammation resolution and tissue regeneration by production of anti-inflammatory cytokines and specialized pro resolving mediators (SPM). Aging is associated with chronic and unresolved, low-grade inflammation (“inflammaging”) and aging-related dysfunction of macrophages in the resolution of inflammation and tissue maintenance has been reported. Yet, the underlying molecular mechanisms and functional consequences of latter processes remain poorly understood. Here, we show that polarization of peritoneal macrophages (PM) from geriatric mice towards an M2-like phenotype is impaired versus adult mice, resulting in aberrant LM formation and cytokine release. In PMs isolated from adult mice (PM-A) we observed a shift in LM formation from PGs and LTs to SPMs already after 4 h of polarization towards M2 with interleukin (IL) 4. In contrast, PMs from geriatric mice (PM-G) produced mainly LTs and PGs upon polarization. This pattern persists over the course of 48 h of polarization. Proteomic profiling revealed that polarization of PM A towards M2 yields a more distinct phenotype, clearly separated from M1, when compared to PM-G. We observed similar aging-related changes in the lipidome and cytokine profile of spleen, lung and liver tissue from mice. Hence, we hypothesize that during aging macrophage polarization towards M2 is impaired, which in turn drives chronic inflammation and disturbs tissue maintenance. By combining state-of-the art lipidomic and proteomic profiling we aim to uncover new molecular targets for pharmaceutical interventions to improve therapeutic strategies for elderly patients with chronic inflammatory diseases.

Dataset Information

Single-cell RNA-seq dictionary of in vivo immune responses to cytokines

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets