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| Status |
Public on Jan 15, 2023 |
| Title |
TGFbR signaling in squamous epithelial cells plays a fundamental role in controlling tissue specific allergic inflammation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Allergic diseases are becoming a global health crisis. Individuals harboring loss-of-function variants in transforming growth factor beta receptor (TGFbR) have an increased prevalence of allergic disease, but the mechanisms responsible are poorly understood. We demonstrate that mice harboring a variant identified in patients spontaneously develop disease that clinically, immunologically, histologically, and transcriptionally recapitulates eosinophilic esophagitis, a condition characterized by allergic inflammation in the esophagus. Diminished TGFbR signaling impairs epithelial cell maturation, resulting in local expression of inflammatory mediators that drive accumulation and activation of eosinophils, mast cells, T cells, and innate lymphoid cells. Our work reveals a fundamental, non-redundant, cell-intrinsic role for TGFbR signaling in epithelial cells needed to maintain immune homeostasis and prevent allergic inflammation, independent of barrier function or adaptive immune tolerance. Moreover, we demonstrate that epithelial dysfunction alone is sufficient to initiate and perpetuate allergic inflammation, which has implications for the prevention and treatment of allergic diseases.
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| Overall design |
18 total samples were mRNA sequenced, with 9 WT, and 9 TGFBR1M318R mutant mice.
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| Web link |
https://www.science.org/doi/10.1126/sciimmunol.abp9940
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| Contributor(s) |
Laky K, Kinard JL, Li JM, Moore IM, Lack JB, Fischer ER, Kabat J, Minai M, Latanich R, Zachos NC, Limkar AR, Rosenberg HF, Thompson RW, Wynn TA, Dietz HC, Guerrerio AL, Frischmeyer-Guerrerio PA |
| Citation(s) |
36608150 |
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| Submission date |
Jan 15, 2022 |
| Last update date |
Apr 17, 2023 |
| Contact name |
Karen Laky |
| E-mail(s) |
klaky@niaid.nih.gov
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| Phone |
301 961-5419
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| Organization name |
NIH
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| Department |
NIAID
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| Lab |
FARS
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| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA797650 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE193756_fpkm.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE193756_raw_counts.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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