BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract againstChlamydia Article Swipe
Miguel A. B. Mercado
,
Qiang Li
,
Charles M. Quick
,
Yejin Kim
,
Rachel S. Palmer
,
Lu Huang
,
Lin‐Xi Li
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.11.02.565369
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.11.02.565369
The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of Bhlhe40 in protective T cell responses to the intracellular bacterium Chlamydia in the female reproductive tract (FRT). Mice deficient in Bhlhe40 exhibited severe defects in their ability to control Chlamydia muridarum shedding from the FRT. The heightened bacterial burdens in Bhlhe40 −/− mice correlated with a marked increase in IL-10-producing T regulatory type 1 (Tr1) cells and decreased polyfunctional CD4 T cells co-producing IFN-γ, IL-17A and GM-CSF. Genetic ablation of IL-10 or functional blockade of IL-10R increased CD4 T cell polyfunctionality and partially rescued the defects in bacterial control in Bhlhe40 −/− mice. Using single-cell RNA sequencing coupled with TCR profiling, we detected a significant enrichment of stem-like T cell signatures in Bhlhe40 -deficient CD4 T cells, whereas WT CD4 T cells were further down on the differentiation trajectory with distinct effector functions beyond IFN-γ production by Th1 cells. Altogether, we identified Bhlhe40 as a key molecular driver of CD4 T cell differentiation and polyfunctional responses in the FRT against Chlamydia .
Related Topics
Concepts
Chlamydia
Biology
Effector
T-cell receptor
T cell
Immunology
Cell biology
Microbiology
Immune system
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.11.02.565369
- https://www.biorxiv.org/content/biorxiv/early/2023/11/05/2023.11.02.565369.full.pdf
- OA Status
- green
- References
- 66
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4388373753
All OpenAlex metadata
Raw OpenAlex JSON
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- DOI
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https://doi.org/10.1101/2023.11.02.565369Digital Object Identifier
- Title
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BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract againstChlamydiaWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-11-05Full publication date if available
- Authors
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Miguel A. B. Mercado, Qiang Li, Charles M. Quick, Yejin Kim, Rachel S. Palmer, Lu Huang, Lin‐Xi LiList of authors in order
- Landing page
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https://doi.org/10.1101/2023.11.02.565369Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2023/11/05/2023.11.02.565369.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2023/11/05/2023.11.02.565369.full.pdfDirect OA link when available
- Concepts
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Chlamydia, Biology, Effector, T-cell receptor, T cell, Immunology, Cell biology, Microbiology, Immune systemTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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66Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| publication_year | 2023 |
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| abstract_inverted_index.In | 28 |
| abstract_inverted_index.WT | 154 |
| abstract_inverted_index.as | 15, 179 |
| abstract_inverted_index.by | 172 |
| abstract_inverted_index.in | 37, 47, 55, 60, 75, 84, 122, 125, 147, 192 |
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| abstract_inverted_index.on | 161 |
| abstract_inverted_index.or | 107 |
| abstract_inverted_index.to | 22, 42, 63 |
| abstract_inverted_index.we | 31, 137, 176 |
| abstract_inverted_index.CD4 | 95, 113, 150, 155, 185 |
| abstract_inverted_index.FRT | 194 |
| abstract_inverted_index.RNA | 131 |
| abstract_inverted_index.TCR | 135 |
| abstract_inverted_index.Th1 | 173 |
| abstract_inverted_index.The | 1, 71 |
| abstract_inverted_index.and | 26, 92, 101, 117, 189 |
| abstract_inverted_index.e40 | 7 |
| abstract_inverted_index.key | 17, 181 |
| abstract_inverted_index.the | 33, 43, 48, 69, 120, 162, 193 |
| abstract_inverted_index.FRT. | 70 |
| abstract_inverted_index.Mice | 53 |
| abstract_inverted_index.cell | 40, 115, 145, 187 |
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| abstract_inverted_index.IL-17A | 100 |
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| abstract_inverted_index.cells. | 174 |
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| abstract_inverted_index.exhibited | 57 |
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| abstract_inverted_index.increased | 112 |
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| abstract_inverted_index.partially | 118 |
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| cited_by_percentile_year | |
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| citation_normalized_percentile.is_in_top_10_percent | False |