An intraepithelial ILC1-like natural killer cell subset produces IL-13
Natural killer (NK) cells are innate immune effectors with considerable heterogeneity and potent antitumor capabilities. Intraepithelial ILC1 (ieILC1)-like NK cells, a population of cytotoxic tissue-resident innate lymphoid cells, have recently been documented in the microenvironment of head and nec...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521086/full |
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| author | Sainiteesh Maddineni Krishna Sharma Imran A. Mohammad Alistaire D. Ruggiero-Sherman Ivan Stepanek June Ho Shin Jennifer K. Bando John B. Sunwoo |
| author_facet | Sainiteesh Maddineni Krishna Sharma Imran A. Mohammad Alistaire D. Ruggiero-Sherman Ivan Stepanek June Ho Shin Jennifer K. Bando John B. Sunwoo |
| author_sort | Sainiteesh Maddineni |
| collection | DOAJ |
| description | Natural killer (NK) cells are innate immune effectors with considerable heterogeneity and potent antitumor capabilities. Intraepithelial ILC1 (ieILC1)-like NK cells, a population of cytotoxic tissue-resident innate lymphoid cells, have recently been documented in the microenvironment of head and neck squamous cell carcinomas (HNSCC) and other solid tumors. These cells have antitumor cytolytic potential and are potent producers of type 1 cytokines, including IFNγ. Here, we identify a subpopulation of ex vivo differentiated ieILC1-like NK cells that produce IL-13 upon stimulation. Functional characterization revealed that these cells co-expressed IFNγ and IL-13 while maintaining an ILC1 transcriptional signature. IL-13 was induced either upon co-culture with tumor cell lines, or in response to TGF-β and IL-15. IL-13-expressing ieILC1-like NK cells were identified among tumor infiltrating lymphocytes expanded from patient HNSCC tumors, in support of their in vivoexistence in primary tumors. These data demonstrate additional heterogeneity within the ieILC1-like NK cell population than previously appreciated and highlight a unique form of ILC plasticity in which cells with clear ILC1 transcriptional profiles express a type 2 cytokine. With the known roles of IL-13 in cancer cell growth dynamics and immunoregulation, the identification of this subset within tumor microenvironments presents a potential target for therapeutic manipulation. |
| format | Article |
| id | doaj-art-cf71f148d17e498e8733ce181dbd5796 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-cf71f148d17e498e8733ce181dbd57962025-08-20T03:02:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15210861521086An intraepithelial ILC1-like natural killer cell subset produces IL-13Sainiteesh Maddineni0Krishna Sharma1Imran A. Mohammad2Alistaire D. Ruggiero-Sherman3Ivan Stepanek4June Ho Shin5Jennifer K. Bando6John B. Sunwoo7Department of Otolaryngology — Head & Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, United StatesDepartment of Otolaryngology — Head & Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, United StatesDepartment of Otolaryngology — Head & Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, United StatesDepartment of Otolaryngology — Head & Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, United StatesDepartment of Otolaryngology — Head & Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, United StatesDepartment of Otolaryngology — Head & Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, United StatesDepartment of Microbiology & Immunology, Stanford University School of Medicine, Palo Alto, CA, United StatesDepartment of Otolaryngology — Head & Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, United StatesNatural killer (NK) cells are innate immune effectors with considerable heterogeneity and potent antitumor capabilities. Intraepithelial ILC1 (ieILC1)-like NK cells, a population of cytotoxic tissue-resident innate lymphoid cells, have recently been documented in the microenvironment of head and neck squamous cell carcinomas (HNSCC) and other solid tumors. These cells have antitumor cytolytic potential and are potent producers of type 1 cytokines, including IFNγ. Here, we identify a subpopulation of ex vivo differentiated ieILC1-like NK cells that produce IL-13 upon stimulation. Functional characterization revealed that these cells co-expressed IFNγ and IL-13 while maintaining an ILC1 transcriptional signature. IL-13 was induced either upon co-culture with tumor cell lines, or in response to TGF-β and IL-15. IL-13-expressing ieILC1-like NK cells were identified among tumor infiltrating lymphocytes expanded from patient HNSCC tumors, in support of their in vivoexistence in primary tumors. These data demonstrate additional heterogeneity within the ieILC1-like NK cell population than previously appreciated and highlight a unique form of ILC plasticity in which cells with clear ILC1 transcriptional profiles express a type 2 cytokine. With the known roles of IL-13 in cancer cell growth dynamics and immunoregulation, the identification of this subset within tumor microenvironments presents a potential target for therapeutic manipulation.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521086/fullNK cellstumor immunologyIL-13cytokinesILCallergy |
| spellingShingle | Sainiteesh Maddineni Krishna Sharma Imran A. Mohammad Alistaire D. Ruggiero-Sherman Ivan Stepanek June Ho Shin Jennifer K. Bando John B. Sunwoo An intraepithelial ILC1-like natural killer cell subset produces IL-13 Frontiers in Immunology NK cells tumor immunology IL-13 cytokines ILC allergy |
| title | An intraepithelial ILC1-like natural killer cell subset produces IL-13 |
| title_full | An intraepithelial ILC1-like natural killer cell subset produces IL-13 |
| title_fullStr | An intraepithelial ILC1-like natural killer cell subset produces IL-13 |
| title_full_unstemmed | An intraepithelial ILC1-like natural killer cell subset produces IL-13 |
| title_short | An intraepithelial ILC1-like natural killer cell subset produces IL-13 |
| title_sort | intraepithelial ilc1 like natural killer cell subset produces il 13 |
| topic | NK cells tumor immunology IL-13 cytokines ILC allergy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1521086/full |
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