TCF1–LEF1 co-expression identifies a multipotent progenitor cell (T(H)2-MPP) across human allergic diseases Journal Article
| Authors: | Kratchmarov, R.; Djeddi, S.; Dunlap, G.; He, W.; Jia, X.; Burk, C. M.; Ryan, T.; McGill, A.; Allegretti, J. R.; Kataru, R. P.; Mehrara, B. J.; Taylor, E. M.; Agarwal, S.; Bhattacharyya, N.; Bergmark, R. W.; Maxfield, A. Z.; Lee, S.; Roditi, R.; Dwyer, D. F.; Boyce, J. A.; Buchheit, K. M.; Laidlaw, T. M.; Shreffler, W. G.; Rao, D. A.; Gutierrez-Arcelus, M.; Brennan, P. J. |
| Article Title: | TCF1–LEF1 co-expression identifies a multipotent progenitor cell (T(H)2-MPP) across human allergic diseases |
| Abstract: | Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells. © Springer Nature America, Inc. 2024. |
| Keywords: | controlled study; human tissue; protein expression; human cell; genetics; flow cytometry; mouse; animal; metabolism; animals; mice; cells, cultured; apoptosis; dexamethasone; in vivo study; cell differentiation; in vitro study; transcriptomics; cell lineage; t lymphocyte receptor; cytokine; regulatory t lymphocyte; th2 cell; immunology; cytokines; cell culture; t-lymphocytes, regulatory; cytokine production; effector cell; immunophenotyping; bioinformatics; multipotent stem cell; multipotent stem cells; t lymphocyte subpopulation; chronic inflammation; transcription factor 7; t cell transcription factor 1; lymphoid enhancer factor 1; lymphoid enhancer-binding factor 1; memory t lymphocyte; stem cell expansion; th2 cells; hypersensitivity; interleukin 4 receptor; thymic stromal lymphopoietin; humans; human; article; stem cell self-renewal; lef1 protein, human; hepatocyte nuclear factor 1alpha; hepatocyte nuclear factor 1-alpha; tfh cell; single cell rna seq; tcf7 protein, human; allergic disease; pathological tissue; rhinosinusitis; t lymphocyte differentiation |
| Journal Title: | Nature Immunology |
| Volume: | 25 |
| Issue: | 5 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-05-01 |
| Start Page: | 902 |
| End Page: | 915 |
| Language: | English |
| DOI: | 10.1038/s41590-024-01803-2 |
| PUBMED: | 38589618 |
| PROVIDER: | scopus |
| PMCID: | PMC11849131 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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