The Transcription Factor RORα Preserves ILC3 Lineage Identity and Function during Chronic Intestinal Infection
| Autor: | T. Michael Underhill, Michael R. Hughes, Diana Canals Hernaez, R. Wilder Scott, Fumio Takei, Kelly M. McNagny, Bernard C. Lo, Samuel B. Shin |
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| Rok vydání: | 2019 |
| Předmět: |
Lymphoid Tissue
medicine.medical_treatment Immunology Biology 03 medical and health sciences Mice 0302 clinical medicine Immunity RAR-related orphan receptor gamma Fibrosis medicine Immunology and Allergy Animals Lymphocytes Receptor Gene Transcription factor Innate lymphoid cell Nuclear Receptor Subfamily 1 Group F Member 1 medicine.disease Enteritis Immunity Innate Cell biology Disease Models Animal Cytokine Chronic Disease Biomarkers 030215 immunology |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 203(12) |
| ISSN: | 1550-6606 |
| Popis: | Innate lymphoid cells (ILCs) are critical for host defense and tissue repair but can also contribute to chronic inflammatory diseases. The transcription factor RORα is required for ILC2 development but is also highly expressed by other ILC subsets where its function remains poorly defined. We previously reported that Rorasg/sg bone marrow chimeric mice (C57BL/6J) were protected from Salmonella-induced intestinal fibrosis due to defective ILC3 responses. In this study, single-cell RNA analysis of ILCs isolated from inflamed tissues indicates that RORα perturbation led to a reduction in ILC3 lineages. Furthermore, residual Rorasg/sg ILC3s have decreased expression of key signature genes, including Rorc and activating cytokine receptors. Collectively, our data suggest that RORα plays a key role in preserving functional ILC3s by modulating their ability to integrate environmental cues to efficiently produce cytokines. |
| Databáze: | OpenAIRE |
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