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Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis
Ting Wen, … , Daniel Douek, Marc E. Rothenberg
Ting Wen, … , Daniel Douek, Marc E. Rothenberg
Published April 8, 2019
Citation Information: J Clin Invest. 2019;129(5):2014-2028. https://doi.org/10.1172/JCI125917.
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Research Article Immunology

Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis

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Abstract

T cell heterogeneity is highly relevant to allergic disorders. We resolved the heterogeneity of human tissue CD3+ T cells during allergic inflammation, focusing on a tissue-specific allergic disease, eosinophilic esophagitis (EoE). We investigated 1088 single T cells derived from patients with a spectrum of disease activity. Eight disparate tissue T cell subtypes (designated T1–T8) were identified, with T7 and T8 enriched in the diseased tissue. The phenotypes of T7 and T8 resemble putative Treg (FOXP3+) and effector Th2-like (GATA3+) cells, respectively. Prodigious levels of IL-5 and IL-13 were confined to HPGDS+ CRTH2+IL-17RB+FFAR3+CD4+ T8 effector Th2 cells. EoE severity closely paralleled a lipid/fatty acid–induced activation node highlighted by the expression of the short-chain fatty acid receptor FFAR3. Ligands for FFAR3 induced Th2 cytokine production from human and murine T cells, including in an in vivo allergy model. Therefore, we elucidated the defining characteristics of tissue-residing CD3+ T cells in EoE, a specific enrichment of CD4+ Treg and effector Th2 cells, confinement of type 2 cytokine production to the CD4+ effector population, a highly likely role for FFAR3 in amplifying local Th2 responses in EoE, and a resource to further dissect tissue lymphocytes and allergic responses.

Authors

Ting Wen, Bruce J. Aronow, Yrina Rochman, Mark Rochman, Kiran KC, Phil J. Dexheimer, Philip Putnam, Vincent Mukkada, Heather Foote, Kira Rehn, Sam Darko, Daniel Douek, Marc E. Rothenberg

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Figure 1

The schematic overall strategy to study tissue lymphocytes.

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The schematic overall strategy to study tissue lymphocytes.
(A) Flow cha...
(A) Flow chart of the overall single-cell platform used to study human tissue lymphocytes, which consists of 3 basic modules: flow cytometry (FACS), bulk CD3+ RNA-seq, and C1 Fluidigm–based single-cell RNA-seq. (B) CD3+ lymphocytes isolated from esophageal biopsy tissue and autologous blood were analyzed by FACS and substratified into CD4+ and CD8+ populations.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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