IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation
Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection, autoimmune disease, and vaccination. In this study, we investigated whether the development and migration of skin-resident DC were regulated by IFN...
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Published in | The Journal of immunology (1950) Vol. 189; no. 7; pp. 3368 - 3377 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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01.10.2012
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Abstract | Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection, autoimmune disease, and vaccination. In this study, we investigated whether the development and migration of skin-resident DC were regulated by IFN regulatory factor 4 (IRF4), a transcription factor that is required for the development of CD11b(+) splenic DC. We found that the skin of naive IRF4(-/-) mice contained normal numbers of epidermal Langerhans cells (eLC) and increased numbers of CD11b(+) and CD103(+) dermal DC (dDC) populations, indicating that tissue DC development and skin residency is not disrupted by IRF4 deficiency. In contrast, numbers of migratory eLC and CD11b(+) dDC were significantly reduced in the cutaneous LN of IRF4(-/-) mice, suggesting a defect in constitutive migration from the dermis during homeostasis. Upon induction of skin inflammation, CD11b(+) dDC in IRF4(-/-) mice did not express the chemokine receptor CCR7 and failed to migrate to cutaneous LN, whereas the migration of eLC was only mildly impaired. Thus, although dispensable for their development, IRF4 is crucial for the CCR7-mediated migration of CD11b(+) dDC, a predominant population in murine and human skin that plays a vital role in normal and pathogenic cutaneous immunity. |
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AbstractList | Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection, autoimmune disease, and vaccination. In this study, we investigated whether the development and migration of skin-resident DC were regulated by IFN regulatory factor 4 (IRF4), a transcription factor that is required for the development of CD11b(+) splenic DC. We found that the skin of naive IRF4(-/-) mice contained normal numbers of epidermal Langerhans cells (eLC) and increased numbers of CD11b(+) and CD103(+) dermal DC (dDC) populations, indicating that tissue DC development and skin residency is not disrupted by IRF4 deficiency. In contrast, numbers of migratory eLC and CD11b(+) dDC were significantly reduced in the cutaneous LN of IRF4(-/-) mice, suggesting a defect in constitutive migration from the dermis during homeostasis. Upon induction of skin inflammation, CD11b(+) dDC in IRF4(-/-) mice did not express the chemokine receptor CCR7 and failed to migrate to cutaneous LN, whereas the migration of eLC was only mildly impaired. Thus, although dispensable for their development, IRF4 is crucial for the CCR7-mediated migration of CD11b(+) dDC, a predominant population in murine and human skin that plays a vital role in normal and pathogenic cutaneous immunity. Abstract Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection, autoimmune disease, and vaccination. In this study, we investigated whether the development and migration of skin-resident DC were regulated by IFN regulatory factor 4 (IRF4), a transcription factor that is required for the development of CD11b+ splenic DC. We found that the skin of naive IRF4−/− mice contained normal numbers of epidermal Langerhans cells (eLC) and increased numbers of CD11b+ and CD103+ dermal DC (dDC) populations, indicating that tissue DC development and skin residency is not disrupted by IRF4 deficiency. In contrast, numbers of migratory eLC and CD11b+ dDC were significantly reduced in the cutaneous LN of IRF4−/− mice, suggesting a defect in constitutive migration from the dermis during homeostasis. Upon induction of skin inflammation, CD11b+ dDC in IRF4−/− mice did not express the chemokine receptor CCR7 and failed to migrate to cutaneous LN, whereas the migration of eLC was only mildly impaired. Thus, although dispensable for their development, IRF4 is crucial for the CCR7-mediated migration of CD11b+ dDC, a predominant population in murine and human skin that plays a vital role in normal and pathogenic cutaneous immunity. |
Author | Kovats, Susan Paul, Jinny Turner, Sean Roach, Kimberly Bajaña, Sandra |
Author_xml | – sequence: 1 givenname: Sandra surname: Bajaña fullname: Bajaña, Sandra organization: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA – sequence: 2 givenname: Kimberly surname: Roach fullname: Roach, Kimberly – sequence: 3 givenname: Sean surname: Turner fullname: Turner, Sean – sequence: 4 givenname: Jinny surname: Paul fullname: Paul, Jinny – sequence: 5 givenname: Susan surname: Kovats fullname: Kovats, Susan |
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Snippet | Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection,... Abstract Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous... |
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SubjectTerms | Animals CD11b Antigen - biosynthesis Cell Movement - immunology Cells, Cultured Dendritic Cells - cytology Dendritic Cells - immunology Dendritic Cells - pathology Female Homeostasis - immunology Inflammation Mediators - metabolism Inflammation Mediators - physiology Interferon Regulatory Factors - deficiency Interferon Regulatory Factors - genetics Interferon Regulatory Factors - physiology Lymph Nodes - cytology Lymph Nodes - immunology Lymph Nodes - pathology Male Mice Mice, Inbred C57BL Mice, Knockout Skin - cytology Skin - immunology Skin - pathology Spleen - cytology Spleen - immunology Spleen - pathology |
Title | IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation |
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