RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T Cells
Thymus-derived natural Foxp3+ CD4+ regulatory T cells (nTregs) play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs) are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DC...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00726/full |
| _version_ | 1828377113034489856 |
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| author | Anja Döhler Theresa Schneider Ina Eckert Eliana Ribechini Nico Andreas Marc Riemann Boris Reizis Falk Weih Manfred B. Lutz |
| author_facet | Anja Döhler Theresa Schneider Ina Eckert Eliana Ribechini Nico Andreas Marc Riemann Boris Reizis Falk Weih Manfred B. Lutz |
| author_sort | Anja Döhler |
| collection | DOAJ |
| description | Thymus-derived natural Foxp3+ CD4+ regulatory T cells (nTregs) play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs) are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DCs manage to keep the peripheral pool at constant levels remain poorly understood. Here, we describe that the NF-κB/Rel family transcription factor RelB controls the frequencies of steady-state migratory DCs (ssmDCs) in peripheral lymph nodes and their numbers control peripheral nTreg homeostasis. DC-specific RelB depletion was investigated in CD11c-Cre × RelBfl/fl mice (RelBDCko), which showed normal frequencies of resident DCs in lymph nodes and spleen while the subsets of CD103− Langerin− dermal DCs (dDCs) and Langerhans cells but not CD103+ Langerin+ dDC of the ssmDCs in skin-draining lymph nodes were increased. Enhanced frequencies and proliferation rates were also observed for nTregs and a small population of CD4+ CD44high CD25low memory-like T cells (Tml). Interestingly, only the Tml but not DCs showed an increase in IL-2-producing capacity in lymph nodes of RelBDCko mice. Blocking of IL-2 in vivo reduced the frequency of nTregs but increased the Tml frequencies, followed by a recovery of nTregs. Taken together, by employing RelBDCko mice with increased frequencies of ssmDCs our data indicate a critical role for specific ssmDC subsets for the peripheral nTreg and IL-2+ Tml frequencies during homeostasis. |
| first_indexed | 2024-04-14T08:09:40Z |
| format | Article |
| id | doaj.art-2a667aeec8c04584bd5bd1e52dbb1a7c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T08:09:40Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2a667aeec8c04584bd5bd1e52dbb1a7c2022-12-22T02:04:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-06-01810.3389/fimmu.2017.00726269100RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T CellsAnja Döhler0Theresa Schneider1Ina Eckert2Eliana Ribechini3Nico Andreas4Marc Riemann5Boris Reizis6Falk Weih7Manfred B. Lutz8Institute for Virology and Immunobiology, University of Würzburg, Würzburg, GermanyInstitute for Virology and Immunobiology, University of Würzburg, Würzburg, GermanyInstitute for Virology and Immunobiology, University of Würzburg, Würzburg, GermanyInstitute for Virology and Immunobiology, University of Würzburg, Würzburg, GermanyLeibniz Institute on Aging – Fritz Lipmann Institute, Jena, GermanyLeibniz Institute on Aging – Fritz Lipmann Institute, Jena, GermanyDepartment of Pathology, Department of Medicine, NYU Langone Medical Center, New York, NY, United StatesLeibniz Institute on Aging – Fritz Lipmann Institute, Jena, GermanyInstitute for Virology and Immunobiology, University of Würzburg, Würzburg, GermanyThymus-derived natural Foxp3+ CD4+ regulatory T cells (nTregs) play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs) are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DCs manage to keep the peripheral pool at constant levels remain poorly understood. Here, we describe that the NF-κB/Rel family transcription factor RelB controls the frequencies of steady-state migratory DCs (ssmDCs) in peripheral lymph nodes and their numbers control peripheral nTreg homeostasis. DC-specific RelB depletion was investigated in CD11c-Cre × RelBfl/fl mice (RelBDCko), which showed normal frequencies of resident DCs in lymph nodes and spleen while the subsets of CD103− Langerin− dermal DCs (dDCs) and Langerhans cells but not CD103+ Langerin+ dDC of the ssmDCs in skin-draining lymph nodes were increased. Enhanced frequencies and proliferation rates were also observed for nTregs and a small population of CD4+ CD44high CD25low memory-like T cells (Tml). Interestingly, only the Tml but not DCs showed an increase in IL-2-producing capacity in lymph nodes of RelBDCko mice. Blocking of IL-2 in vivo reduced the frequency of nTregs but increased the Tml frequencies, followed by a recovery of nTregs. Taken together, by employing RelBDCko mice with increased frequencies of ssmDCs our data indicate a critical role for specific ssmDC subsets for the peripheral nTreg and IL-2+ Tml frequencies during homeostasis.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00726/fulldendritic cellsRelBregulatory T cellsIL-2lymph nodes |
| spellingShingle | Anja Döhler Theresa Schneider Ina Eckert Eliana Ribechini Nico Andreas Marc Riemann Boris Reizis Falk Weih Manfred B. Lutz RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T Cells Frontiers in Immunology dendritic cells RelB regulatory T cells IL-2 lymph nodes |
| title | RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T Cells |
| title_full | RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T Cells |
| title_fullStr | RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T Cells |
| title_full_unstemmed | RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T Cells |
| title_short | RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T Cells |
| title_sort | relb steady state migratory dendritic cells control the peripheral pool of the natural foxp3 regulatory t cells |
| topic | dendritic cells RelB regulatory T cells IL-2 lymph nodes |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00726/full |
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