PMID- 33098765
OWN - NLM
STAT- MEDLINE
DCOM- 20210430
LR  - 20211118
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 53
IP  - 5
DP  - 2020 Nov 17
TI  - Substance P Release by Sensory Neurons Triggers Dendritic Cell Migration and 
      Initiates the Type-2 Immune Response to Allergens.
PG  - 1063-1077.e7
LID - S1074-7613(20)30413-1 [pii]
LID - 10.1016/j.immuni.2020.10.001 [doi]
AB  - Dendritic cells (DCs) of the cDC2 lineage initiate allergic immunity and in the 
      dermis are marked by their expression of CD301b. CD301b(+) dermal DCs respond to 
      allergens encountered in vivo, but not in vitro. This suggests that another cell 
      in the dermis may sense allergens and relay that information to activate and 
      induce the migration of CD301b(+) DCs to the draining lymph node (dLN). Using a 
      model of cutaneous allergen exposure, we show that allergens directly activated 
      TRPV1(+) sensory neurons leading to itch and pain behaviors. Allergen-activated 
      sensory neurons released the neuropeptide Substance P, which stimulated 
      proximally located CD301b(+) DCs through the Mas-related G-protein coupled 
      receptor member A1 (MRGPRA1). Substance P induced CD301b(+) DC migration to the 
      dLN where they initiated T helper-2 cell differentiation. Thus, sensory neurons 
      act as primary sensors of allergens, linking exposure to activation of 
      allergic-skewing DCs and the initiation of an allergic immune response.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Perner, Caroline
AU  - Perner C
AD  - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 
      Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA 02114, USA.
FAU - Flayer, Cameron H
AU  - Flayer CH
AD  - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 
      Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA 02114, USA.
FAU - Zhu, Xueping
AU  - Zhu X
AD  - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 
      Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA 02114, USA.
FAU - Aderhold, Pamela A
AU  - Aderhold PA
AD  - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 
      Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA 02114, USA.
FAU - Dewan, Zaynah N A
AU  - Dewan ZNA
AD  - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 
      Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA 02114, USA.
FAU - Voisin, Tiphaine
AU  - Voisin T
AD  - Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
FAU - Camire, Ryan B
AU  - Camire RB
AD  - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 
      Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA 02114, USA; Department of Immunology, Harvard Medical School, Boston, 
      MA 02115, USA.
FAU - Chow, Ohn A
AU  - Chow OA
AD  - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 
      Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA 02114, USA.
FAU - Chiu, Isaac M
AU  - Chiu IM
AD  - Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
FAU - Sokol, Caroline L
AU  - Sokol CL
AD  - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, 
      Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA 02114, USA. Electronic address: clsokol@mgh.harvard.edu.
LA  - eng
GR  - R01 AI130019/AI/NIAID NIH HHS/United States
GR  - S10 RR023440/RR/NCRR NIH HHS/United States
GR  - S10 RR020936/RR/NCRR NIH HHS/United States
GR  - T32 HL116275/HL/NHLBI NIH HHS/United States
GR  - S10 OD016372/OD/NIH HHS/United States
GR  - S10 OD012027/OD/NIH HHS/United States
GR  - DP2 AT009499/AT/NCCIH NIH HHS/United States
GR  - K08 AI121421/AI/NIAID NIH HHS/United States
GR  - P30 DK043351/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201023
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Allergens)
RN  - 0 (Biomarkers)
RN  - 33507-63-0 (Substance P)
SB  - IM
CIN - Immunity. 2020 Nov 17;53(5):900-902. PMID: 33207213
MH  - Allergens/*immunology
MH  - Animals
MH  - Biomarkers
MH  - Cell Movement/immunology
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Female
MH  - Ganglia, Spinal/cytology
MH  - Hypersensitivity/diagnosis/*etiology/*metabolism
MH  - Male
MH  - Mice
MH  - Sensory Receptor Cells/immunology/*metabolism
MH  - Substance P/*biosynthesis
PMC - PMC7677179
MID - NIHMS1636724
OTO - NOTNLM
OT  - MRGPRA1
OT  - Substance P
OT  - TRPV1
OT  - Th2
OT  - allergy
OT  - chemotaxis
OT  - dendritic cells
OT  - sensory neurons
COIS- Declaration of Interests C.L.S. is a paid consultant for Bayer and Merck. P.A.A. 
      is a current employee of Skyhawk Therapeutics. I.M.C. receives sponsored research 
      support from GSK and Allergan Pharmaceuticals. I.M.C. is on the scientific 
      advisory boards of GSK and Kintai Pharmaceuticals.
EDAT- 2020/10/26 06:00
MHDA- 2021/05/01 06:00
PMCR- 2021/11/17
CRDT- 2020/10/25 00:00
PHST- 2020/04/02 00:00 [received]
PHST- 2020/07/21 00:00 [revised]
PHST- 2020/09/30 00:00 [accepted]
PHST- 2020/10/26 06:00 [pubmed]
PHST- 2021/05/01 06:00 [medline]
PHST- 2020/10/25 00:00 [entrez]
PHST- 2021/11/17 00:00 [pmc-release]
AID - S1074-7613(20)30413-1 [pii]
AID - 10.1016/j.immuni.2020.10.001 [doi]
PST - ppublish
SO  - Immunity. 2020 Nov 17;53(5):1063-1077.e7. doi: 10.1016/j.immuni.2020.10.001. Epub 
      2020 Oct 23.