Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway
Proliferation of dendritic cell (DC)—restricted progenitor cells in bone marrow compartment is tightly regulated at steady state and responds to multiple tissue-specific triggers during disturbed homeostasis such as obesity. DCs in the lung stem from a rapidly dividing DC-restricted progenitor cells...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00363/full |
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| author | Anil Kumar Jaiswal Anil Kumar Jaiswal Sangeet Makhija Sangeet Makhija Natalie Stahr Natalie Stahr Maninder Sandey Amol Suryawanshi Ankit Saxena Pradeep K. Dagur J. Philip McCoy Stewart J. Levine Amarjit Mishra Amarjit Mishra |
| author_facet | Anil Kumar Jaiswal Anil Kumar Jaiswal Sangeet Makhija Sangeet Makhija Natalie Stahr Natalie Stahr Maninder Sandey Amol Suryawanshi Ankit Saxena Pradeep K. Dagur J. Philip McCoy Stewart J. Levine Amarjit Mishra Amarjit Mishra |
| author_sort | Anil Kumar Jaiswal |
| collection | DOAJ |
| description | Proliferation of dendritic cell (DC)—restricted progenitor cells in bone marrow compartment is tightly regulated at steady state and responds to multiple tissue-specific triggers during disturbed homeostasis such as obesity. DCs in the lung stem from a rapidly dividing DC-restricted progenitor cells and are effective at generating adaptive immune responses in allergic airway inflammation. Precisely, how DC-restricted progenitor expansion and differentiation are influenced by airway inflammation to maintain constant supply of myeloid DCs is poorly understood. Here we show that a high fat diet (HFD) induces oxidative stress and accelerates the expansion of DC- restricted progenitor cells in bone marrow and correlates with persistent induction of p38 mitogen activated protein kinase (MAPK), which is blocked with a selective p38α/β MAPK inhibitor. Mice fed a HFD and sensitized to inhaled allergen house dust mite (HDM) led to alterations of DC- restricted progenitor cells that were characterized by increased expansion and seeding of lung DCs in airway inflammation. Mechanistically, we establish that the expansion induced by HFD dysregulates the expression of a disintegrin and metallopeptidase domain 17 (Adam17) and is required for p38 MAPK activation in DC-restricted progenitors. These results demonstrates that obesity produces persistent changes in DC precursors and that elevation of Adam17 expression is tightly coupled to p38 MAPK and is a key driver of proliferation. Altogether, these data provide phenotypic and mechanistic insight into dendritic cell supply chain in obesity-associated airway inflammation. |
| first_indexed | 2024-12-12T22:38:00Z |
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| id | doaj.art-ac3586ca0a3a42f0adc320c4da9ef968 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T22:38:00Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ac3586ca0a3a42f0adc320c4da9ef9682022-12-22T00:09:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00363513309Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent PathwayAnil Kumar Jaiswal0Anil Kumar Jaiswal1Sangeet Makhija2Sangeet Makhija3Natalie Stahr4Natalie Stahr5Maninder Sandey6Amol Suryawanshi7Ankit Saxena8Pradeep K. Dagur9J. Philip McCoy10Stewart J. Levine11Amarjit Mishra12Amarjit Mishra13Laboratory of Lung Inflammation, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesLaboratory of Lung Inflammation, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesLaboratory of Lung Inflammation, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesFlow Cytometry Core Facility, Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, United StatesFlow Cytometry Core Facility, Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, United StatesFlow Cytometry Core Facility, Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, United StatesLaboratory of Asthma and Lung Inflammation, Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, United StatesLaboratory of Lung Inflammation, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United StatesProliferation of dendritic cell (DC)—restricted progenitor cells in bone marrow compartment is tightly regulated at steady state and responds to multiple tissue-specific triggers during disturbed homeostasis such as obesity. DCs in the lung stem from a rapidly dividing DC-restricted progenitor cells and are effective at generating adaptive immune responses in allergic airway inflammation. Precisely, how DC-restricted progenitor expansion and differentiation are influenced by airway inflammation to maintain constant supply of myeloid DCs is poorly understood. Here we show that a high fat diet (HFD) induces oxidative stress and accelerates the expansion of DC- restricted progenitor cells in bone marrow and correlates with persistent induction of p38 mitogen activated protein kinase (MAPK), which is blocked with a selective p38α/β MAPK inhibitor. Mice fed a HFD and sensitized to inhaled allergen house dust mite (HDM) led to alterations of DC- restricted progenitor cells that were characterized by increased expansion and seeding of lung DCs in airway inflammation. Mechanistically, we establish that the expansion induced by HFD dysregulates the expression of a disintegrin and metallopeptidase domain 17 (Adam17) and is required for p38 MAPK activation in DC-restricted progenitors. These results demonstrates that obesity produces persistent changes in DC precursors and that elevation of Adam17 expression is tightly coupled to p38 MAPK and is a key driver of proliferation. Altogether, these data provide phenotypic and mechanistic insight into dendritic cell supply chain in obesity-associated airway inflammation.https://www.frontiersin.org/article/10.3389/fimmu.2020.00363/fulldendritic cell-restricted progenitorsCDPsobesityasthmaAdam17p38 MAPK pathway |
| spellingShingle | Anil Kumar Jaiswal Anil Kumar Jaiswal Sangeet Makhija Sangeet Makhija Natalie Stahr Natalie Stahr Maninder Sandey Amol Suryawanshi Ankit Saxena Pradeep K. Dagur J. Philip McCoy Stewart J. Levine Amarjit Mishra Amarjit Mishra Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway Frontiers in Immunology dendritic cell-restricted progenitors CDPs obesity asthma Adam17 p38 MAPK pathway |
| title | Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway |
| title_full | Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway |
| title_fullStr | Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway |
| title_full_unstemmed | Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway |
| title_short | Dendritic Cell-Restricted Progenitors Contribute to Obesity-Associated Airway Inflammation via Adam17-p38 MAPK-Dependent Pathway |
| title_sort | dendritic cell restricted progenitors contribute to obesity associated airway inflammation via adam17 p38 mapk dependent pathway |
| topic | dendritic cell-restricted progenitors CDPs obesity asthma Adam17 p38 MAPK pathway |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00363/full |
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