Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and Cancer
Colony-stimulating factor 1 (CSF1) and interleukin 34 (IL34) signal via the CSF1 receptor to regulate macrophage differentiation. Studies in IL34- or CSF1-deficient mice have revealed that IL34 function is limited to the central nervous system and skin during development. However, the roles of IL34...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02019/full |
| _version_ | 1818013046737469440 |
|---|---|
| author | WeiYu Lin Daqi Xu Cary D. Austin Patrick Caplazi Kate Senger Yonglian Sun Surinder Jeet Judy Young Donnie Delarosa Eric Suto Zhiyu Huang Juan Zhang Donghong Yan Cesar Corzo Kai Barck Sharmila Rajan Carrie Looney Vineela Gandham Justin Lesch Wei-Ching Liang Elaine Mai Hai Ngu Navneet Ratti Yongmei Chen Dinah Misner Tori Lin Dimitry Danilenko Paula Katavolos Estelle Doudemont Hirdesh Uppal Jeffrey Eastham Judy Mak Patricia E. de Almeida Katherine Bao Azadeh Hadadianpour Mary Keir Richard A. D. Carano Lauri Diehl Min Xu Yan Wu Robby M. Weimer Jason DeVoss Wyne P. Lee Mercedesz Balazs Kevin Walsh Kathila R. Alatsis Flavius Martin Ali A. Zarrin |
| author_facet | WeiYu Lin Daqi Xu Cary D. Austin Patrick Caplazi Kate Senger Yonglian Sun Surinder Jeet Judy Young Donnie Delarosa Eric Suto Zhiyu Huang Juan Zhang Donghong Yan Cesar Corzo Kai Barck Sharmila Rajan Carrie Looney Vineela Gandham Justin Lesch Wei-Ching Liang Elaine Mai Hai Ngu Navneet Ratti Yongmei Chen Dinah Misner Tori Lin Dimitry Danilenko Paula Katavolos Estelle Doudemont Hirdesh Uppal Jeffrey Eastham Judy Mak Patricia E. de Almeida Katherine Bao Azadeh Hadadianpour Mary Keir Richard A. D. Carano Lauri Diehl Min Xu Yan Wu Robby M. Weimer Jason DeVoss Wyne P. Lee Mercedesz Balazs Kevin Walsh Kathila R. Alatsis Flavius Martin Ali A. Zarrin |
| author_sort | WeiYu Lin |
| collection | DOAJ |
| description | Colony-stimulating factor 1 (CSF1) and interleukin 34 (IL34) signal via the CSF1 receptor to regulate macrophage differentiation. Studies in IL34- or CSF1-deficient mice have revealed that IL34 function is limited to the central nervous system and skin during development. However, the roles of IL34 and CSF1 at homeostasis or in the context of inflammatory diseases or cancer in wild-type mice have not been clarified in vivo. By neutralizing CSF1 and/or IL34 in adult mice, we identified that they play important roles in macrophage differentiation, specifically in steady-state microglia, Langerhans cells, and kidney macrophages. In several inflammatory models, neutralization of both CSF1 and IL34 contributed to maximal disease protection. However, in a myeloid cell-rich tumor model, CSF1 but not IL34 was required for tumor-associated macrophage accumulation and immune homeostasis. Analysis of human inflammatory conditions reveals IL34 upregulation that may account for the protection requirement of IL34 blockade. Furthermore, evaluation of IL34 and CSF1 blockade treatment during Listeria infection reveals no substantial safety concerns. Thus, IL34 and CSF1 play non-redundant roles in macrophage differentiation, and therapeutic intervention targeting IL34 and/or CSF1 may provide an effective treatment in macrophage-driven immune-pathologies. |
| first_indexed | 2024-04-14T06:28:27Z |
| format | Article |
| id | doaj.art-f5bbd900f7f94b86b15fbd853c8ad352 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T06:28:27Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f5bbd900f7f94b86b15fbd853c8ad3522022-12-22T02:07:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-09-011010.3389/fimmu.2019.02019479204Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and CancerWeiYu LinDaqi XuCary D. AustinPatrick CaplaziKate SengerYonglian SunSurinder JeetJudy YoungDonnie DelarosaEric SutoZhiyu HuangJuan ZhangDonghong YanCesar CorzoKai BarckSharmila RajanCarrie LooneyVineela GandhamJustin LeschWei-Ching LiangElaine MaiHai NguNavneet RattiYongmei ChenDinah MisnerTori LinDimitry DanilenkoPaula KatavolosEstelle DoudemontHirdesh UppalJeffrey EasthamJudy MakPatricia E. de AlmeidaKatherine BaoAzadeh HadadianpourMary KeirRichard A. D. CaranoLauri DiehlMin XuYan WuRobby M. WeimerJason DeVossWyne P. LeeMercedesz BalazsKevin WalshKathila R. AlatsisFlavius MartinAli A. ZarrinColony-stimulating factor 1 (CSF1) and interleukin 34 (IL34) signal via the CSF1 receptor to regulate macrophage differentiation. Studies in IL34- or CSF1-deficient mice have revealed that IL34 function is limited to the central nervous system and skin during development. However, the roles of IL34 and CSF1 at homeostasis or in the context of inflammatory diseases or cancer in wild-type mice have not been clarified in vivo. By neutralizing CSF1 and/or IL34 in adult mice, we identified that they play important roles in macrophage differentiation, specifically in steady-state microglia, Langerhans cells, and kidney macrophages. In several inflammatory models, neutralization of both CSF1 and IL34 contributed to maximal disease protection. However, in a myeloid cell-rich tumor model, CSF1 but not IL34 was required for tumor-associated macrophage accumulation and immune homeostasis. Analysis of human inflammatory conditions reveals IL34 upregulation that may account for the protection requirement of IL34 blockade. Furthermore, evaluation of IL34 and CSF1 blockade treatment during Listeria infection reveals no substantial safety concerns. Thus, IL34 and CSF1 play non-redundant roles in macrophage differentiation, and therapeutic intervention targeting IL34 and/or CSF1 may provide an effective treatment in macrophage-driven immune-pathologies.https://www.frontiersin.org/article/10.3389/fimmu.2019.02019/fullCSF1 and Il34 inhibitioncancerinflammationmacrophagemonocyteCSF1R |
| spellingShingle | WeiYu Lin Daqi Xu Cary D. Austin Patrick Caplazi Kate Senger Yonglian Sun Surinder Jeet Judy Young Donnie Delarosa Eric Suto Zhiyu Huang Juan Zhang Donghong Yan Cesar Corzo Kai Barck Sharmila Rajan Carrie Looney Vineela Gandham Justin Lesch Wei-Ching Liang Elaine Mai Hai Ngu Navneet Ratti Yongmei Chen Dinah Misner Tori Lin Dimitry Danilenko Paula Katavolos Estelle Doudemont Hirdesh Uppal Jeffrey Eastham Judy Mak Patricia E. de Almeida Katherine Bao Azadeh Hadadianpour Mary Keir Richard A. D. Carano Lauri Diehl Min Xu Yan Wu Robby M. Weimer Jason DeVoss Wyne P. Lee Mercedesz Balazs Kevin Walsh Kathila R. Alatsis Flavius Martin Ali A. Zarrin Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and Cancer Frontiers in Immunology CSF1 and Il34 inhibition cancer inflammation macrophage monocyte CSF1R |
| title | Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and Cancer |
| title_full | Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and Cancer |
| title_fullStr | Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and Cancer |
| title_full_unstemmed | Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and Cancer |
| title_short | Function of CSF1 and IL34 in Macrophage Homeostasis, Inflammation, and Cancer |
| title_sort | function of csf1 and il34 in macrophage homeostasis inflammation and cancer |
| topic | CSF1 and Il34 inhibition cancer inflammation macrophage monocyte CSF1R |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02019/full |
| work_keys_str_mv | AT weiyulin functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT daqixu functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT carydaustin functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT patrickcaplazi functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT katesenger functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT yongliansun functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT surinderjeet functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT judyyoung functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT donniedelarosa functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT ericsuto functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT zhiyuhuang functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT juanzhang functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT donghongyan functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT cesarcorzo functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT kaibarck functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT sharmilarajan functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT carrielooney functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT vineelagandham functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT justinlesch functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT weichingliang functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT elainemai functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT haingu functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT navneetratti functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT yongmeichen functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT dinahmisner functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT torilin functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT dimitrydanilenko functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT paulakatavolos functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT estelledoudemont functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT hirdeshuppal functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT jeffreyeastham functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT judymak functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT patriciaedealmeida functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT katherinebao functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT azadehhadadianpour functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT marykeir functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT richardadcarano functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT lauridiehl functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT minxu functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT yanwu functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT robbymweimer functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT jasondevoss functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT wyneplee functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT mercedeszbalazs functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT kevinwalsh functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT kathilaralatsis functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT flaviusmartin functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer AT aliazarrin functionofcsf1andil34inmacrophagehomeostasisinflammationandcancer |