PMID- 35778404
OWN - NLM
STAT- MEDLINE
DCOM- 20220707
LR  - 20240206
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Jul 1
TI  - Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of 
      IL-9.
PG  - 3811
LID - 10.1038/s41467-022-31596-7 [doi]
LID - 3811
AB  - Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, 
      some models suggest that it can promote tumor growth. Here, we show that IL-9 
      signaling is associated with poor outcomes in patients with various forms of lung 
      cancer, and is required for lung tumor growth in multiple mouse models. CD4(+) T 
      cell-derived IL-9 promotes the expansion of both CD11c(+) and CD11c(-) 
      interstitial macrophage populations in lung tumor models. Mechanistically, the 
      IL-9/macrophage axis requires arginase 1 (Arg1) to mediate tumor growth. Indeed, 
      adoptive transfer of Arg1(+) but not Arg1(-) lung macrophages to Il9r(-/-) mice 
      promotes tumor growth. Moreover, targeting IL-9 signaling using 
      macrophage-specific nanoparticles restricts lung tumor growth in mice. Lastly, 
      elevated expression of IL-9R and Arg1 in tumor lesions is associated with poor 
      prognosis in lung cancer patients. Thus, our study suggests the 
      IL-9/macrophage/Arg1 axis is a potential therapeutic target for lung cancer 
      therapy.
CI  - (c) 2022. The Author(s).
FAU - Fu, Yongyao
AU  - Fu Y
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine, 
      Indianapolis, IN, 46202, USA.
FAU - Pajulas, Abigail
AU  - Pajulas A
AUID- ORCID: 0000-0002-1137-1400
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine, 
      Indianapolis, IN, 46202, USA.
FAU - Wang, Jocelyn
AU  - Wang J
AUID- ORCID: 0000-0003-0016-3136
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine, 
      Indianapolis, IN, 46202, USA.
FAU - Zhou, Baohua
AU  - Zhou B
AUID- ORCID: 0000-0003-1156-4517
AD  - Department of Pediatrics and Herman B Wells Center for Pediatric Research, 
      Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
FAU - Cannon, Anthony
AU  - Cannon A
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine, 
      Indianapolis, IN, 46202, USA.
FAU - Cheung, Cherry Cheuk Lam
AU  - Cheung CCL
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine, 
      Indianapolis, IN, 46202, USA.
FAU - Zhang, Jilu
AU  - Zhang J
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine, 
      Indianapolis, IN, 46202, USA.
FAU - Zhou, Huaxin
AU  - Zhou H
AD  - Division of Pulmonary, Critical Care, Sleep and Occupational Medicine/Department 
      of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
FAU - Fisher, Amanda Jo
AU  - Fisher AJ
AD  - Division of Pulmonary, Critical Care, Sleep and Occupational Medicine/Department 
      of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
FAU - Omstead, David T
AU  - Omstead DT
AD  - Department of Chemical and Biomolecular Engineering, University of Notre Dame, 
      Notre Dame, IN, 46556, USA.
FAU - Khan, Sabrina
AU  - Khan S
AUID- ORCID: 0000-0002-0531-897X
AD  - Department of Chemical and Biomolecular Engineering, University of Notre Dame, 
      Notre Dame, IN, 46556, USA.
FAU - Han, Lei
AU  - Han L
AD  - Department of Pediatrics and Herman B Wells Center for Pediatric Research, 
      Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
FAU - Renauld, Jean-Christophe
AU  - Renauld JC
AD  - Ludwig Institute for Cancer Research, Experimental Medicine Unit, Universite 
      Catholique de Louvain, Brussels, 1200, Belgium.
FAU - Paczesny, Sophie
AU  - Paczesny S
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      173 Ashley Avenue, Charleston, SC, 29425, USA.
FAU - Gao, Hongyu
AU  - Gao H
AD  - Department of Medical and Molecular Genetics, Indiana University School of 
      Medicine, Indianapolis, IN, 46202, USA.
FAU - Liu, Yunlong
AU  - Liu Y
AUID- ORCID: 0000-0002-2699-626X
AD  - Department of Medical and Molecular Genetics, Indiana University School of 
      Medicine, Indianapolis, IN, 46202, USA.
FAU - Yang, Lei
AU  - Yang L
AD  - Department of Pediatrics and Herman B Wells Center for Pediatric Research, 
      Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
FAU - Tighe, Robert M
AU  - Tighe RM
AUID- ORCID: 0000-0002-3465-9861
AD  - Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University 
      Medical Center, Durham, NC, 27710, USA.
FAU - Licona-Limon, Paula
AU  - Licona-Limon P
AD  - Departamento de Biologia Celular y del Desarrollo, Instituto de Fisiologia 
      Celular, Universidad Nacional Autonoma de Mexico, 04510, Mexico City, Mexico.
FAU - Flavell, Richard A
AU  - Flavell RA
AUID- ORCID: 0000-0003-4461-0778
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 
      06510, USA.
FAU - Takatsuka, Shogo
AU  - Takatsuka S
AD  - Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, 
      Noda, Japan.
FAU - Kitamura, Daisuke
AU  - Kitamura D
AUID- ORCID: 0000-0002-5195-0474
AD  - Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, 
      Noda, Japan.
FAU - Sun, Jie
AU  - Sun J
AUID- ORCID: 0000-0002-2347-4511
AD  - Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
FAU - Bilgicer, Basar
AU  - Bilgicer B
AD  - Department of Chemical and Biomolecular Engineering, University of Notre Dame, 
      Notre Dame, IN, 46556, USA.
FAU - Sears, Catherine R
AU  - Sears CR
AUID- ORCID: 0000-0002-5797-3458
AD  - Division of Pulmonary, Critical Care, Sleep and Occupational Medicine/Department 
      of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
FAU - Yang, Kai
AU  - Yang K
AD  - Department of Pediatrics and Herman B Wells Center for Pediatric Research, 
      Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
FAU - Kaplan, Mark H
AU  - Kaplan MH
AUID- ORCID: 0000-0002-2923-8245
AD  - Department of Microbiology and Immunology, Indiana University School of Medicine, 
      Indianapolis, IN, 46202, USA. mkaplan2@iupui.edu.
LA  - eng
GR  - R01 AI085046/AI/NIAID NIH HHS/United States
GR  - T32 HL007910/HL/NHLBI NIH HHS/United States
GR  - R01 AI129241/AI/NIAID NIH HHS/United States
GR  - U01 CA232491/CA/NCI NIH HHS/United States
GR  - P20 GM121176/GM/NIGMS NIH HHS/United States
GR  - R01 HL158096/HL/NHLBI NIH HHS/United States
GR  - T32 AI060519/AI/NIAID NIH HHS/United States
GR  - I01 BX005353/BX/BLRD VA/United States
PT  - Journal Article
DEP - 20220701
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (IL9 protein, human)
RN  - 0 (Interleukin-9)
SB  - IM
MH  - Animals
MH  - Carcinogenesis/metabolism
MH  - *Interleukin-9/genetics/metabolism
MH  - *Lung Neoplasms/metabolism/pathology
MH  - *Macrophages/metabolism/pathology
MH  - Macrophages, Alveolar/metabolism
MH  - Mice
PMC - PMC9249769
COIS- D.T.O., S.K., B.B., Y.F., and M.H.K. are authors on pending patent applications 
      for nanoparticle approaches. R.A.F. is an advisor to Glaxo Smith Kline, Zai Lab, 
      and Ventus Therapeutics though not in the context of this work. The remaining 
      authors declare no competing interests.
EDAT- 2022/07/02 06:00
MHDA- 2022/07/08 06:00
PMCR- 2022/07/01
CRDT- 2022/07/01 23:16
PHST- 2021/07/17 00:00 [received]
PHST- 2022/06/21 00:00 [accepted]
PHST- 2022/07/01 23:16 [entrez]
PHST- 2022/07/02 06:00 [pubmed]
PHST- 2022/07/08 06:00 [medline]
PHST- 2022/07/01 00:00 [pmc-release]
AID - 10.1038/s41467-022-31596-7 [pii]
AID - 31596 [pii]
AID - 10.1038/s41467-022-31596-7 [doi]
PST - epublish
SO  - Nat Commun. 2022 Jul 1;13(1):3811. doi: 10.1038/s41467-022-31596-7.