PMID- 37562753
OWN - NLM
STAT- MEDLINE
DCOM- 20231113
LR  - 20240309
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 152
IP  - 5
DP  - 2023 Nov
TI  - Complement C1q essential for aeroallergen sensitization via CSF1R(+) conventional 
      dendritic cells type 2.
PG  - 1141-1152.e2
LID - S0091-6749(23)00983-1 [pii]
LID - 10.1016/j.jaci.2023.07.016 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) are heterogeneous, comprising multiple subsets 
      with unique functional specifications. Our previous work has demonstrated that 
      the specific conventional type 2 DC subset, CSF1R(+)cDC2s, plays a critical role 
      in sensing aeroallergens. OBJECTIVE: It remains to be understood how 
      CSF1R(+)cDC2s recognize inhaled allergens. We sought to elucidate the 
      transcriptomic programs and receptor-ligand interactions essential for function 
      of this subset in allergen sensitization. METHODS: We applied single-cell RNA 
      sequencing to mouse lung DCs. Conventional DC-selective knockout mouse models 
      were employed, and mice were subjected to inhaled allergen sensitization with 
      multiple readouts of asthma pathology. Under the clinical arm of this work, human 
      lung transcriptomic data were integrated with mouse data, and bronchoalveolar 
      lavage (BAL) specimens were collected from subjects undergoing allergen 
      provocation, with samples assayed for C1q. RESULTS: We found that C1q is 
      selectively enriched in lung CSF1R(+)cDC2s, but not in other lung cDC2 or cDC1 
      subsets. Depletion of C1q in conventional DCs significantly attenuates allergen 
      sensing and features of asthma. Additionally, we found that C1q binds directly to 
      human dust mite allergen, and the C1q receptor CD91 (LRP1) is required for lung 
      CSF1R(+)cDC2s to recognize the C1q-allergen complex and induce allergic lung 
      inflammation. Lastly, C1q is enriched in human BAL samples following subsegmental 
      allergen challenge, and human RNA sequencing data demonstrate close homology 
      between lung IGSF21(+)DCs and mouse CSF1R(+)cDC2s. CONCLUSIONS: C1q is secreted 
      from the CSF1R(+)cDC2 subset among conventional DCs. Our data indicate that the 
      C1q-LRP1 axis represents a candidate for translational therapeutics in the 
      prevention and suppression of allergic lung inflammation.
CI  - Published by Elsevier Inc.
FAU - Moon, Hyung-Geun
AU  - Moon HG
AD  - Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, 
      University of Illinois at Chicago, Chicago. Electronic address: hmoon22@uic.edu.
FAU - Eccles, Jacob D
AU  - Eccles JD
AD  - Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, 
      University of Illinois at Chicago, Chicago.
FAU - Kim, Seung-Jae
AU  - Kim SJ
AD  - Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, 
      University of Illinois at Chicago, Chicago.
FAU - Kim, Ki-Hyun
AU  - Kim KH
AD  - Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, 
      University of Illinois at Chicago, Chicago.
FAU - Kim, Young-Mee
AU  - Kim YM
AD  - Department of Pharmacology, University of Illinois College of Medicine, Chicago.
FAU - Rehman, Jalees
AU  - Rehman J
AD  - Department of Pharmacology, University of Illinois College of Medicine, Chicago.
FAU - Lee, Hyun
AU  - Lee H
AD  - College of Pharmacy, University of Illinois at Chicago, Chicago.
FAU - Kanabar, Pinal
AU  - Kanabar P
AD  - Research Informatics Core, University of Illinois at Chicago, Chicago.
FAU - Christman, John W
AU  - Christman JW
AD  - Section of Pulmonary, Critical Care, and Sleep Medicine, Columbus; Davis Heart 
      and Lung Research Center, The Ohio State University, Columbus.
FAU - Ackerman, Steven J
AU  - Ackerman SJ
AD  - Department of Biochemistry and Molecular Genetics, University of Illinois at 
      Chicago, Chicago; Department of Medicine, University of Illinois at Chicago, 
      Chicago.
FAU - Ascoli, Christian
AU  - Ascoli C
AD  - Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, 
      University of Illinois at Chicago, Chicago.
FAU - Kang, Homan
AU  - Kang H
AD  - Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General 
      Hospital, Harvard Medical School, Boston.
FAU - Choi, Hak Soo
AU  - Choi HS
AD  - Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General 
      Hospital, Harvard Medical School, Boston.
FAU - Kim, Minhyung
AU  - Kim M
AD  - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles; Department of 
      Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles.
FAU - You, Sungyong
AU  - You S
AD  - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles; Department of 
      Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles.
FAU - Park, Gye Young
AU  - Park GY
AD  - Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, 
      University of Illinois at Chicago, Chicago; Jesse Brown Veterans Affairs Medical 
      Center, Chicago. Electronic address: parkgy@uic.edu.
LA  - eng
GR  - KL2 TR002002/TR/NCATS NIH HHS/United States
GR  - R01 HL153170/HL/NHLBI NIH HHS/United States
GR  - R01 HL137224/HL/NHLBI NIH HHS/United States
GR  - UL1 TR002003/TR/NCATS NIH HHS/United States
GR  - P01 HL151327/HL/NHLBI NIH HHS/United States
GR  - I01 BX004981/BX/BLRD VA/United States
GR  - R21 AI171517/AI/NIAID NIH HHS/United States
GR  - R01 HL126852/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230808
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Allergens)
RN  - 80295-33-6 (Complement C1q)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - 0 (Receptors, Colony-Stimulating Factor)
RN  - 0 (C1qa protein, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Allergens/metabolism
MH  - *Asthma/metabolism
MH  - Complement C1q/metabolism
MH  - Dendritic Cells
MH  - Mice, Knockout
MH  - *Pneumonia/metabolism
MH  - Receptor Protein-Tyrosine Kinases
MH  - Receptors, Colony-Stimulating Factor/metabolism
PMC - PMC10923196
MID - NIHMS1924221
OTO - NOTNLM
OT  - Colony stimulating factor 1 receptor (CSF1R)
OT  - allergen sensing
OT  - allergic asthma
OT  - complement component 1q (C1q)
OT  - conventional dendritic cell type 2 (cDC2)
EDAT- 2023/08/11 00:42
MHDA- 2023/11/07 06:45
PMCR- 2024/11/01
CRDT- 2023/08/10 19:29
PHST- 2023/01/27 00:00 [received]
PHST- 2023/06/29 00:00 [revised]
PHST- 2023/07/20 00:00 [accepted]
PHST- 2024/11/01 00:00 [pmc-release]
PHST- 2023/11/07 06:45 [medline]
PHST- 2023/08/11 00:42 [pubmed]
PHST- 2023/08/10 19:29 [entrez]
AID - S0091-6749(23)00983-1 [pii]
AID - 10.1016/j.jaci.2023.07.016 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2023 Nov;152(5):1141-1152.e2. doi: 
      10.1016/j.jaci.2023.07.016. Epub 2023 Aug 8.