Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses
Signaling abnormalities in immune responses in the small intestine can trigger chronic type 2 inflammation involving interaction of multiple immune cell types. To systematically characterize this response, we analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA sequencing (...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/126748 |
| _version_ | 1826196063192612864 |
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| author | Xu, Heping Ding, Jiarui Porter, Caroline Wallrapp, Antonia Tabaka, Marcin Ma, Sai Fu, Shujie Guo, Xuanxuan Riesenfeld, Samantha J. Su, Chienwen Dionne, Danielle Nguyen, Lan T. Lefkovith, Ariel Ashenberg, Orr Burkett, Patrick R. Shi, Hai Ning Rozenblatt-Rosen, Orit Graham, Daniel B. Kuchroo, Vijay K. Regev, Aviv Xavier, Ramnik J. |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Xu, Heping Ding, Jiarui Porter, Caroline Wallrapp, Antonia Tabaka, Marcin Ma, Sai Fu, Shujie Guo, Xuanxuan Riesenfeld, Samantha J. Su, Chienwen Dionne, Danielle Nguyen, Lan T. Lefkovith, Ariel Ashenberg, Orr Burkett, Patrick R. Shi, Hai Ning Rozenblatt-Rosen, Orit Graham, Daniel B. Kuchroo, Vijay K. Regev, Aviv Xavier, Ramnik J. |
| author_sort | Xu, Heping |
| collection | MIT |
| description | Signaling abnormalities in immune responses in the small intestine can trigger chronic type 2 inflammation involving interaction of multiple immune cell types. To systematically characterize this response, we analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA sequencing (scRNA-seq) at steady state and after induction of a type 2 inflammatory reaction to ovalbumin (OVA). Computational analysis revealed broad shifts in both cell-type composition and cell programs in response to the inflammation, especially in group 2 innate lymphoid cells (ILC2s). Inflammation induced the expression of exon 5 of Calca, which encodes the alpha-calcitonin gene-related peptide (α-CGRP), in intestinal KLRG1+ ILC2s. α-CGRP antagonized KLRG1+ ILC2s proliferation but promoted IL-5 expression. Genetic perturbation of α-CGRP increased the proportion of intestinal KLRG1+ ILC2s. Our work highlights a model where α-CGRP-mediated neuronal signaling is critical for suppressing ILC2 expansion and maintaining homeostasis of the type 2 immune machinery. |
| first_indexed | 2024-09-23T10:20:17Z |
| format | Article |
| id | mit-1721.1/126748 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:20:17Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1267482022-09-26T17:19:35Z Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses Xu, Heping Ding, Jiarui Porter, Caroline Wallrapp, Antonia Tabaka, Marcin Ma, Sai Fu, Shujie Guo, Xuanxuan Riesenfeld, Samantha J. Su, Chienwen Dionne, Danielle Nguyen, Lan T. Lefkovith, Ariel Ashenberg, Orr Burkett, Patrick R. Shi, Hai Ning Rozenblatt-Rosen, Orit Graham, Daniel B. Kuchroo, Vijay K. Regev, Aviv Xavier, Ramnik J. Broad Institute of MIT and Harvard Massachusetts Institute of Technology. Department of Biology Signaling abnormalities in immune responses in the small intestine can trigger chronic type 2 inflammation involving interaction of multiple immune cell types. To systematically characterize this response, we analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA sequencing (scRNA-seq) at steady state and after induction of a type 2 inflammatory reaction to ovalbumin (OVA). Computational analysis revealed broad shifts in both cell-type composition and cell programs in response to the inflammation, especially in group 2 innate lymphoid cells (ILC2s). Inflammation induced the expression of exon 5 of Calca, which encodes the alpha-calcitonin gene-related peptide (α-CGRP), in intestinal KLRG1+ ILC2s. α-CGRP antagonized KLRG1+ ILC2s proliferation but promoted IL-5 expression. Genetic perturbation of α-CGRP increased the proportion of intestinal KLRG1+ ILC2s. Our work highlights a model where α-CGRP-mediated neuronal signaling is critical for suppressing ILC2 expansion and maintaining homeostasis of the type 2 immune machinery. 2020-08-24T15:19:40Z 2020-08-24T15:19:40Z 2019-10 2019-08 2020-08-20T17:45:10Z Article http://purl.org/eprint/type/JournalArticle 1074-7613 https://hdl.handle.net/1721.1/126748 Xu, Heping et al. "Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses." Immunity 51, 4 (October 2019): P696-708.e9 © 2019 Elsevier en http://dx.doi.org/10.1016/j.immuni.2019.09.004 Immunity Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Prof. Regev via Courtney Crummett |
| spellingShingle | Xu, Heping Ding, Jiarui Porter, Caroline Wallrapp, Antonia Tabaka, Marcin Ma, Sai Fu, Shujie Guo, Xuanxuan Riesenfeld, Samantha J. Su, Chienwen Dionne, Danielle Nguyen, Lan T. Lefkovith, Ariel Ashenberg, Orr Burkett, Patrick R. Shi, Hai Ning Rozenblatt-Rosen, Orit Graham, Daniel B. Kuchroo, Vijay K. Regev, Aviv Xavier, Ramnik J. Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses |
| title | Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses |
| title_full | Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses |
| title_fullStr | Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses |
| title_full_unstemmed | Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses |
| title_short | Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses |
| title_sort | transcriptional atlas of intestinal immune cells reveals that neuropeptide α cgrp modulates group 2 innate lymphoid cell responses |
| url | https://hdl.handle.net/1721.1/126748 |
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