MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation
Langerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-β and related downstream signaling pathways are known to cont...
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MDPI AG
2023-06-01
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| Online Access: | https://www.mdpi.com/2079-7737/12/7/925 |
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| author | Jie Wang Nirmal Parajuli Qiyan Wang Namir Khalasawi Hongmei Peng Jun Zhang Congcong Yin Qing-Sheng Mi Li Zhou |
| author_facet | Jie Wang Nirmal Parajuli Qiyan Wang Namir Khalasawi Hongmei Peng Jun Zhang Congcong Yin Qing-Sheng Mi Li Zhou |
| author_sort | Jie Wang |
| collection | DOAJ |
| description | Langerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-β and related downstream signaling pathways are known to control numerous aspects of LC biology, little is known about the epigenetic signals that coordinate cell signaling during LC ontogeny, maintenance, and function. Our previous studies in a total miRNA deletion mouse model showed that miRNAs are critically involved in embryonic LC development and postnatal LC homeostasis; however, the specific miRNA(s) that regulate LCs remain unknown. miR-23a is the first member of the miR-23a-27a-24-2 cluster, a direct downstream target of PU.1 and TGF-b, which regulate the determination of myeloid versus lymphoid fates. Therefore, we used a myeloid-specific miR-23a deletion mouse model to explore whether and how miR-23a affects LC ontogeny and function in the skin. We observed the indispensable role of miR-23a in LC antigen uptake and inflammation-induced LC epidermal repopulation; however, embryonic LC development and postnatal homeostasis were not affected by cells lacking miR23a. Our results suggest that miR-23a controls LC phagocytosis by targeting molecules that regulate efferocytosis and endocytosis, whereas miR-23a promotes homeostasis in bone marrow-derived LCs that repopulate the skin after inflammatory insult by targeting Fas and Bcl-2 family proapoptotic molecules. Collectively, the context-dependent regulatory role of miR-23a in LCs represents an extra-epigenetic layer that incorporates TGF-b- and PU.1-mediated regulation during steady-state and inflammation-induced repopulation. |
| first_indexed | 2024-03-11T01:17:33Z |
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| language | English |
| last_indexed | 2024-03-11T01:17:33Z |
| publishDate | 2023-06-01 |
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| series | Biology |
| spelling | doaj.art-5ae3f681bdb94564b3ec673c3eaa80072023-11-18T18:23:08ZengMDPI AGBiology2079-77372023-06-0112792510.3390/biology12070925MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell RepopulationJie Wang0Nirmal Parajuli1Qiyan Wang2Namir Khalasawi3Hongmei Peng4Jun Zhang5Congcong Yin6Qing-Sheng Mi7Li Zhou8Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USACenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USACenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USACenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USACenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USACenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USACenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USACenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USACenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USALangerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-β and related downstream signaling pathways are known to control numerous aspects of LC biology, little is known about the epigenetic signals that coordinate cell signaling during LC ontogeny, maintenance, and function. Our previous studies in a total miRNA deletion mouse model showed that miRNAs are critically involved in embryonic LC development and postnatal LC homeostasis; however, the specific miRNA(s) that regulate LCs remain unknown. miR-23a is the first member of the miR-23a-27a-24-2 cluster, a direct downstream target of PU.1 and TGF-b, which regulate the determination of myeloid versus lymphoid fates. Therefore, we used a myeloid-specific miR-23a deletion mouse model to explore whether and how miR-23a affects LC ontogeny and function in the skin. We observed the indispensable role of miR-23a in LC antigen uptake and inflammation-induced LC epidermal repopulation; however, embryonic LC development and postnatal homeostasis were not affected by cells lacking miR23a. Our results suggest that miR-23a controls LC phagocytosis by targeting molecules that regulate efferocytosis and endocytosis, whereas miR-23a promotes homeostasis in bone marrow-derived LCs that repopulate the skin after inflammatory insult by targeting Fas and Bcl-2 family proapoptotic molecules. Collectively, the context-dependent regulatory role of miR-23a in LCs represents an extra-epigenetic layer that incorporates TGF-b- and PU.1-mediated regulation during steady-state and inflammation-induced repopulation.https://www.mdpi.com/2079-7737/12/7/925miR-23aLangerhans cellsskin |
| spellingShingle | Jie Wang Nirmal Parajuli Qiyan Wang Namir Khalasawi Hongmei Peng Jun Zhang Congcong Yin Qing-Sheng Mi Li Zhou MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation Biology miR-23a Langerhans cells skin |
| title | MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation |
| title_full | MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation |
| title_fullStr | MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation |
| title_full_unstemmed | MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation |
| title_short | MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation |
| title_sort | mir 23a regulates skin langerhans cell phagocytosis and inflammation induced langerhans cell repopulation |
| topic | miR-23a Langerhans cells skin |
| url | https://www.mdpi.com/2079-7737/12/7/925 |
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