PMID- 31371561
OWN - NLM
STAT- MEDLINE
DCOM- 20200304
LR  - 20230511
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 365
IP  - 6456
DP  - 2019 Aug 30
TI  - Identification of a T follicular helper cell subset that drives anaphylactic IgE.
LID - 10.1126/science.aaw6433 [doi]
LID - eaaw6433
AB  - Cross-linking of high-affinity immunoglobulin E (IgE) results in the 
      life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that 
      induce B cells to produce IgE in response to allergens remain poorly understood. 
      T follicular helper (T(FH)) cells direct the affinity and isotype of antibodies 
      produced by B cells. Although T(FH) cell-derived interleukin-4 (IL-4) is 
      necessary for IgE production, it is not sufficient. We report a rare population 
      of IL-13-producing T(FH) cells present in mice and humans with IgE to allergens, 
      but not when allergen-specific IgE was absent or only low-affinity. These 
      "T(FH)13" cells have an unusual cytokine profile 
      (IL-13(hi)IL-4(hi)IL-5(hi)IL-21(lo)) and coexpress the transcription factors BCL6 
      and GATA3. T(FH)13 cells are required for production of high- but not 
      low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking T(FH)13 
      cells may represent an alternative therapeutic target to ameliorate anaphylaxis.
CI  - Copyright (c) 2019 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Gowthaman, Uthaman
AU  - Gowthaman U
AUID- ORCID: 0000-0002-5484-7851
AD  - Department of Laboratory Medicine, Yale University School of Medicine, New Haven, 
      CT 06520, USA.
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Chen, Jennifer S
AU  - Chen JS
AUID- ORCID: 0000-0002-7808-2670
AD  - Department of Laboratory Medicine, Yale University School of Medicine, New Haven, 
      CT 06520, USA.
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Zhang, Biyan
AU  - Zhang B
AUID- ORCID: 0000-0003-0329-2451
AD  - Department of Laboratory Medicine, Yale University School of Medicine, New Haven, 
      CT 06520, USA.
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Flynn, William F
AU  - Flynn WF
AUID- ORCID: 0000-0001-6533-0340
AD  - The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
FAU - Lu, Yisi
AU  - Lu Y
AUID- ORCID: 0000-0002-7960-5445
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Song, Wenzhi
AU  - Song W
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Joseph, Julie
AU  - Joseph J
AD  - Department of Laboratory Medicine, Yale University School of Medicine, New Haven, 
      CT 06520, USA.
FAU - Gertie, Jake A
AU  - Gertie JA
AUID- ORCID: 0000-0002-3867-1884
AD  - Department of Laboratory Medicine, Yale University School of Medicine, New Haven, 
      CT 06520, USA.
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Xu, Lan
AU  - Xu L
AUID- ORCID: 0000-0002-9909-7660
AD  - Department of Laboratory Medicine, Yale University School of Medicine, New Haven, 
      CT 06520, USA.
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Collet, Magalie A
AU  - Collet MA
AUID- ORCID: 0000-0002-7200-345X
AD  - The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
FAU - Grassmann, Jessica D S
AU  - Grassmann JDS
AUID- ORCID: 0000-0001-9076-452X
AD  - The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
FAU - Simoneau, Tregony
AU  - Simoneau T
AUID- ORCID: 0000-0003-2407-4402
AD  - The Asthma Center, CT Children's Medical Center, Hartford, CT 06106, USA.
FAU - Chiang, David
AU  - Chiang D
AUID- ORCID: 0000-0002-3844-6126
AD  - Jaffe Food Allergy Institute and Precision Immunology Institute, Icahn School of 
      Medicine at Mount Sinai, New York, NY 10029, USA.
FAU - Berin, M Cecilia
AU  - Berin MC
AUID- ORCID: 0000-0002-9051-9249
AD  - Jaffe Food Allergy Institute and Precision Immunology Institute, Icahn School of 
      Medicine at Mount Sinai, New York, NY 10029, USA.
FAU - Craft, Joseph E
AU  - Craft JE
AUID- ORCID: 0000-0002-1368-6756
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Weinstein, Jason S
AU  - Weinstein JS
AD  - Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, 
      NJ 07101, USA.
FAU - Williams, Adam
AU  - Williams A
AUID- ORCID: 0000-0002-5151-4103
AD  - The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA. 
      stephanie.eisenbarth@yale.edu adam.williams@jax.org.
AD  - The Department of Genetics and Genome Sciences, University of Connecticut Health 
      Center, Farmington, CT 06032, USA.
FAU - Eisenbarth, Stephanie C
AU  - Eisenbarth SC
AUID- ORCID: 0000-0002-1244-208X
AD  - Department of Laboratory Medicine, Yale University School of Medicine, New Haven, 
      CT 06520, USA. stephanie.eisenbarth@yale.edu adam.williams@jax.org.
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
LA  - eng
GR  - R37 AR040072/AR/NIAMS NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - R01 AI108829/AI/NIAID NIH HHS/United States
GR  - R21 AI133440/AI/NIAID NIH HHS/United States
GR  - R01 AI136942/AI/NIAID NIH HHS/United States
GR  - R21 AI135221/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190801
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Dock8 protein, mouse)
RN  - 0 (GATA3 Transcription Factor)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Interleukin-13)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
CIN - Trends Pharmacol Sci. 2019 Oct;40(10):714-716. PMID: 31493932
MH  - Adolescent
MH  - Anaphylaxis/*immunology
MH  - Animals
MH  - Child
MH  - GATA3 Transcription Factor/metabolism
MH  - Guanine Nucleotide Exchange Factors/genetics/metabolism
MH  - Humans
MH  - Immunoglobulin E/*immunology
MH  - Interleukin-13/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Proto-Oncogene Proteins c-bcl-6/metabolism
MH  - T-Lymphocytes, Helper-Inducer/*immunology
PMC - PMC6901029
MID - NIHMS1058199
EDAT- 2019/08/03 06:00
MHDA- 2020/03/05 06:00
PMCR- 2020/08/30
CRDT- 2019/08/03 06:00
PHST- 2019/01/28 00:00 [received]
PHST- 2019/07/18 00:00 [accepted]
PHST- 2019/08/03 06:00 [pubmed]
PHST- 2020/03/05 06:00 [medline]
PHST- 2019/08/03 06:00 [entrez]
PHST- 2020/08/30 00:00 [pmc-release]
AID - science.aaw6433 [pii]
AID - 10.1126/science.aaw6433 [doi]
PST - ppublish
SO  - Science. 2019 Aug 30;365(6456):eaaw6433. doi: 10.1126/science.aaw6433. Epub 2019 
      Aug 1.