Tolerance to 2,4-dinitrofluorobenzene-induced contact hypersensitivity is mediated by CD73-expressing tissue-homing regulatory T cells
Regulatory T cells (Tregs) express CD73, an ectonucleotidase that converts adenosine (Ado) monophosphate to Ado, which has been shown to suppress immune reactions. To investigate the role(s) of CD73+ Tregs during the induction of tolerance, we used a 2,4-dinitrofluorobenzene‒driven contact hypersens...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 2023
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| In: |
The journal of investigative dermatology
Year: 2023, Volume: 143, Issue: 6, Pages: 1011-1022.e8 |
| ISSN: | 1523-1747 |
| DOI: | 10.1016/j.jid.2022.12.003 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jid.2022.12.003 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022202X22028871 
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| Author Notes: | Meihong Da, Luxia Chen, Alexander Enk and Karsten Mahnke |
| Summary: | Regulatory T cells (Tregs) express CD73, an ectonucleotidase that converts adenosine (Ado) monophosphate to Ado, which has been shown to suppress immune reactions. To investigate the role(s) of CD73+ Tregs during the induction of tolerance, we used a 2,4-dinitrofluorobenzene‒driven contact hypersensitivity model, in which tolerance can be induced by pretreating wild type mice with 2,4-dinitrothiocyanobenzene. CD73-deficient mice were unable to acquire tolerance. Likewise, transfer of CD73‒/‒ Tregs failed to suppress 2,4-dinitrofluorobenzene‒induced ear swelling in wild type mice, whereas transfer of wild type‒derived Tregs into CD73‒/‒ mice re-established tolerance. This indicates a crucial role of CD73+ Tregs for skin-induced tolerance. Furthermore, we found that 2,4-dinitrothiocyanobenzene induces more activated CD73+ tissue-homing Tregs (marked by Ki-67, CTLA4, CCR4, CD103, CCR6, and CD49b expression) in draining lymph nodes and blood, eventually accumulating in the skin. The application of anti-CD73 antibodies that block CD73-derived Ado production as well as the injection of Ado deaminase, which degrades Ado in tissues, abrogated tolerance induction. Thus, our data indicate that CD73+ Ado-producing Tregs are crucial for the regulation of contact hypersensitivity reactions and tolerance induction in the skin and that manipulating the function(s) of CD73 in tissues may offer a tool to influence autoimmunity and inflammation in vivo. |
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| Item Description: | Online verfügbar 17. Dezember 2022, Artikelversion 19 May 2023 Gesehen am 20.07.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1523-1747 |
| DOI: | 10.1016/j.jid.2022.12.003 |