Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis
Adult human skin contains nearly twice as many T cells as the peripheral blood, which include tissue-resident memory T cells. However, the precise mechanisms maintaining tissue-resident memory T cells in the healthy skin remain unclear. Using normal human skin samples, we find that Langerhans cells...
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Elsevier
2025-01-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026724000729 |
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| author | Tomonori Oka Tatsuya Hasegawa Truelian Lee Valeria S. Oliver-Garcia Mahsa Mortaja Marjan Azin Satoshi Horiba Sabrina S. Smith Sara Khattab Kathryn E. Trerice Steven T. Chen Yevgeniy R. Semenov Shadmehr Demehri |
| author_facet | Tomonori Oka Tatsuya Hasegawa Truelian Lee Valeria S. Oliver-Garcia Mahsa Mortaja Marjan Azin Satoshi Horiba Sabrina S. Smith Sara Khattab Kathryn E. Trerice Steven T. Chen Yevgeniy R. Semenov Shadmehr Demehri |
| author_sort | Tomonori Oka |
| collection | DOAJ |
| description | Adult human skin contains nearly twice as many T cells as the peripheral blood, which include tissue-resident memory T cells. However, the precise mechanisms maintaining tissue-resident memory T cells in the healthy skin remain unclear. Using normal human skin samples, we find that Langerhans cells (LCs) contact T cells in the epidermis of the elderly. LCs with high HLA-II, CD86, and PD-L2 expression directly contacted PD-1+ tissue-resident memory T cells and CTLA-4+ regulatory T cells in the epidermis, indicating an axis of peripheral tolerance in a steady state. Environmental insults, UVB radiation, and hapten downregulated HLA-II and CD86 on LCs in the epidermis, suggesting that disruption of LC–T cell tolerogenic axis contributes to skin inflammation. Interestingly, immune checkpoint blockade therapy was associated with decreased epidermal LC–T cell contact in the normal skin of patients with cancer affected by cutaneous immune-related adverse events. Collectively, our findings indicate that LCs may contribute to T cell tolerance in the epidermis. |
| format | Article |
| id | doaj-art-c8c93490ea764a77b1fdd0f1902d549c |
| institution | Kabale University |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-c8c93490ea764a77b1fdd0f1902d549c2025-01-11T06:42:11ZengElsevierJID Innovations2667-02672025-01-0151100324Langerhans Cells Directly Interact with Resident T Cells in the Human EpidermisTomonori Oka0Tatsuya Hasegawa1Truelian Lee2Valeria S. Oliver-Garcia3Mahsa Mortaja4Marjan Azin5Satoshi Horiba6Sabrina S. Smith7Sara Khattab8Kathryn E. Trerice9Steven T. Chen10Yevgeniy R. Semenov11Shadmehr Demehri12Center for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USACenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Shiseido Global Innovation Center, Yokohama, JapanCenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USACenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USACenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USACenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USACenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Shiseido Global Innovation Center, Yokohama, JapanCenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USACenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USACenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USADepartment of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USADepartment of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, USACenter for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Correspondence: Shadmehr Demehri, Department of Dermatology, Massachusetts General Hospital, Building 149 13th Street, 3rd floor, Charlestown, Massachusetts 02129, USA.Adult human skin contains nearly twice as many T cells as the peripheral blood, which include tissue-resident memory T cells. However, the precise mechanisms maintaining tissue-resident memory T cells in the healthy skin remain unclear. Using normal human skin samples, we find that Langerhans cells (LCs) contact T cells in the epidermis of the elderly. LCs with high HLA-II, CD86, and PD-L2 expression directly contacted PD-1+ tissue-resident memory T cells and CTLA-4+ regulatory T cells in the epidermis, indicating an axis of peripheral tolerance in a steady state. Environmental insults, UVB radiation, and hapten downregulated HLA-II and CD86 on LCs in the epidermis, suggesting that disruption of LC–T cell tolerogenic axis contributes to skin inflammation. Interestingly, immune checkpoint blockade therapy was associated with decreased epidermal LC–T cell contact in the normal skin of patients with cancer affected by cutaneous immune-related adverse events. Collectively, our findings indicate that LCs may contribute to T cell tolerance in the epidermis.http://www.sciencedirect.com/science/article/pii/S2667026724000729Immune checkpointLangerhans cellPeripheral toleranceRegulatory T cellTissue-resident memory T cell |
| spellingShingle | Tomonori Oka Tatsuya Hasegawa Truelian Lee Valeria S. Oliver-Garcia Mahsa Mortaja Marjan Azin Satoshi Horiba Sabrina S. Smith Sara Khattab Kathryn E. Trerice Steven T. Chen Yevgeniy R. Semenov Shadmehr Demehri Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis JID Innovations Immune checkpoint Langerhans cell Peripheral tolerance Regulatory T cell Tissue-resident memory T cell |
| title | Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis |
| title_full | Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis |
| title_fullStr | Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis |
| title_full_unstemmed | Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis |
| title_short | Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis |
| title_sort | langerhans cells directly interact with resident t cells in the human epidermis |
| topic | Immune checkpoint Langerhans cell Peripheral tolerance Regulatory T cell Tissue-resident memory T cell |
| url | http://www.sciencedirect.com/science/article/pii/S2667026724000729 |
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