PMID- 36975775
OWN - NLM
STAT- MEDLINE
DCOM- 20230330
LR  - 20230410
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 131
IP  - 3
DP  - 2023 Mar
TI  - Multidimensional Analysis of Lung Lymph Nodes in a Mouse Model of Allergic Lung 
      Inflammation following PM2.5 and Indeno[1,2,3-cd]pyrene Exposure.
PG  - 37014
LID - 10.1289/EHP11580 [doi]
LID - 037014
AB  - BACKGROUND: Ambient particulate matter with an aerodynamic diameter of  </= 2.5 mum 
      (PM2.5) is suggested to act as an adjuvant for allergen-mediated sensitization 
      and recent evidence suggests the importance of T follicular helper (Tfh) cells in 
      allergic diseases. However, the impact of PM2.5 exposure and its absorbed 
      polycyclic aromatic hydrocarbon (PAHs) on Tfh cells and humoral immunity remains 
      unknown. OBJECTIVES: We aimed to explore the impact of environmental PM2.5 and 
      indeno[1,2,3-cd]pyrene (IP), a prominent PAH, as a model, on Tfh cells and the 
      subsequent pulmonary allergic responses. METHODS: PM2.5- or IP-mediated 
      remodeling of cellular composition in lung lymph nodes (LNs) was determined by 
      mass cytometry in a house dust mite (HDM)-induced mouse allergic lung 
      inflammation model. The differentiation and function of Tfh cells in vitro were 
      analyzed by flow cytometry, quantitative reverse transcription polymerase chain 
      reaction, enzyme-linked immunosorbent assay, chromatin immunoprecipitation, 
      immunoprecipitation, and western blot analyses. RESULTS: Mice exposed to PM2.5 
      during the HDM sensitization period demonstrated immune cell population shifts in 
      lung LNs as compared with those sensitized with HDM alone, with a greater number 
      of differentiated Tfh2 cells, enhanced allergen-induced immunoglobulin E (IgE) 
      response and pulmonary inflammation. Similarly enhanced phenotypes were also 
      found in mice exposed to IP and sensitized with HDM. Further, IP administration 
      was found to induce interleukin-21 (Il21) and Il4 expression and enhance Tfh2 
      cell differentiation in vitro, a finding which was abrogated in aryl hydrocarbon 
      receptor (AhR)-deficient CD4+ T cells. Moreover, we showed that IP exposure 
      increased the interaction of AhR and cellular musculoaponeurotic fibrosarcoma 
      (c-Maf) and its occupancy on the Il21 and Il4 promoters in differentiated Tfh2 
      cells. DISCUSSION: These findings suggest that the PM2.5 (IP)-AhR-c-Maf axis in 
      Tfh2 cells was important in allergen sensitization and lung inflammation, thus 
      adding a new dimension in the understanding of Tfh2 cell differentiation and 
      function and providing a basis for establishing the environment-disease causal 
      relationship. https://doi.org/10.1289/EHP11580.
FAU - Liu, Kwei-Yan
AU  - Liu KY
AD  - Department of Respirology & Allergy, Third Affiliated Hospital of Shenzhen 
      University, Shenzhen, China.
AD  - Institute of Pediatrics, Children's Hospital of Fudan University, National 
      Children's Medical Center, and the Shanghai Key Laboratory of Medical 
      Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, 
      Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan 
      University, Shanghai, China.
AD  - National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan 
      University, Shanghai, China.
FAU - Gao, Yajing
AU  - Gao Y
AUID- ORCID: 0000-0002-1639-7909
AD  - Institute of Pediatrics, Children's Hospital of Fudan University, National 
      Children's Medical Center, and the Shanghai Key Laboratory of Medical 
      Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, 
      Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan 
      University, Shanghai, China.
AD  - National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan 
      University, Shanghai, China.
FAU - Xiao, Wenfeng
AU  - Xiao W
AD  - Institute of Pediatrics, Children's Hospital of Fudan University, National 
      Children's Medical Center, and the Shanghai Key Laboratory of Medical 
      Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, 
      Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan 
      University, Shanghai, China.
AD  - National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan 
      University, Shanghai, China.
FAU - Fu, Jinrong
AU  - Fu J
AD  - Institute of Pediatrics, Children's Hospital of Fudan University, National 
      Children's Medical Center, and the Shanghai Key Laboratory of Medical 
      Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, 
      Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan 
      University, Shanghai, China.
AD  - Department of General Medicine, Children's Hospital of Fudan University, 
      Shanghai, China.
FAU - Huang, Saihua
AU  - Huang S
AD  - Institute of Pediatrics, Children's Hospital of Fudan University, National 
      Children's Medical Center, and the Shanghai Key Laboratory of Medical 
      Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, 
      Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan 
      University, Shanghai, China.
AD  - National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan 
      University, Shanghai, China.
FAU - Han, Xiao
AU  - Han X
AD  - Institute of Pediatrics, Children's Hospital of Fudan University, National 
      Children's Medical Center, and the Shanghai Key Laboratory of Medical 
      Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, 
      Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan 
      University, Shanghai, China.
AD  - National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan 
      University, Shanghai, China.
FAU - Hsu, Shih-Hsien
AU  - Hsu SH
AD  - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan.
FAU - Xiao, Xiaojun
AU  - Xiao X
AD  - Institute of Allergy and Immunology, School of Medicine, Shenzhen University, 
      Shenzhen, China.
FAU - Huang, Shau-Ku
AU  - Huang SK
AD  - Department of Respirology & Allergy, Third Affiliated Hospital of Shenzhen 
      University, Shenzhen, China.
AD  - Institute of Allergy and Immunology, School of Medicine, Shenzhen University, 
      Shenzhen, China.
AD  - National Institute of Environmental Health Sciences, National Health Research 
      Institutes, Taiwan.
AD  - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Zhou, Yufeng
AU  - Zhou Y
AUID- ORCID: 0000-0002-6050-4951
AD  - Institute of Pediatrics, Children's Hospital of Fudan University, National 
      Children's Medical Center, and the Shanghai Key Laboratory of Medical 
      Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, 
      Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan 
      University, Shanghai, China.
AD  - National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230328
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 207137-56-2 (Interleukin-4)
RN  - 0 (Allergens)
RN  - 0 (Pyrenes)
SB  - IM
CIN - Environ Health Perspect. 2023 Mar;131(3):31307. PMID: 36975774
MH  - Mice
MH  - Animals
MH  - Interleukin-4
MH  - Lung/pathology
MH  - *Hypersensitivity/genetics/pathology
MH  - Disease Models, Animal
MH  - *Pneumonia/chemically induced
MH  - Allergens/toxicity
MH  - Lymph Nodes/pathology
MH  - Pyroglyphidae
MH  - Pyrenes
PMC - PMC10044348
EDAT- 2023/03/29 06:00
MHDA- 2023/03/30 06:11
PMCR- 2023/03/28
CRDT- 2023/03/28 09:53
PHST- 2023/03/30 06:11 [medline]
PHST- 2023/03/28 09:53 [entrez]
PHST- 2023/03/29 06:00 [pubmed]
PHST- 2023/03/28 00:00 [pmc-release]
AID - EHP11580 [pii]
AID - 10.1289/EHP11580 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2023 Mar;131(3):37014. doi: 10.1289/EHP11580. Epub 2023 
      Mar 28.