PMID- 35536993
OWN - NLM
STAT- MEDLINE
DCOM- 20220627
LR  - 20221108
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 208
IP  - 3
DP  - 2022 Jun 23
TI  - Intravenous immunoglobulin induces IgG internalization by tolerogenic myeloid 
      dendritic cells that secrete IL-10 and expand Fc-specific regulatory T cells.
PG  - 361-371
LID - 10.1093/cei/uxac046 [doi]
AB  - Intravenous immunoglobulin (IVIG) is used as an immunomodulatory agent in many 
      inflammatory conditions including Multisystem Inflammatory Syndrome-Children 
      (MIS-C) and Kawasaki disease (KD). However, the exact mechanisms underlying its 
      anti-inflammatory action are incompletely characterized. Here, we show that in 
      KD, a pediatric acute vasculitis that affects the coronary arteries, IVIG induces 
      a repertoire of natural Treg that recognize immunodominant peptides in the Fc 
      heavy chain constant region. To address which antigen-presenting cell (APC) 
      populations present Fc peptides to Treg, we studied the uptake of IgG by innate 
      cells in subacute KD patients 2 weeks after IVIG and in children 1.6-14 years 
      after KD. Healthy adults served as controls. IgG at high concentrations was 
      internalized predominantly by two myeloid dendritic cell (DC) lineages, CD14+ 
      cDC2 and ILT-4+ CD4+ tmDC mostly through Fcgamma receptor (R) II and to a lesser 
      extent FcgammaRIII. Following IgG internalization, these two DC lineages secreted 
      IL-10 and presented processed Fc peptides to Treg. The validation of IVIG 
      function in expanding Fc-specific Treg presented by CD14+ cDC2 and ILT-4+ CD4+ 
      tmDC was addressed in a small cohort of patients with MIS-C. Taken together, 
      these results suggest a novel immune regulatory function of IgG in activating 
      tolerogenic innate cells and expanding Treg, which reveals an important 
      anti-inflammatory mechanism of action of IVIG.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      British Society for Immunology.
FAU - Hsieh, Li-En
AU  - Hsieh LE
AUID- ORCID: 0000-0003-1179-2229
AD  - University of California San Diego, School of Medicine, Department of Pediatrics, 
      La Jolla, CA 92093-0641, USA.
FAU - Song, Jaeyoon
AU  - Song J
AD  - University of California San Diego, School of Medicine, Department of Pediatrics, 
      La Jolla, CA 92093-0641, USA.
FAU - Tremoulet, Adriana H
AU  - Tremoulet AH
AD  - University of California San Diego, School of Medicine, Department of Pediatrics, 
      La Jolla, CA 92093-0641, USA.
AD  - Rady Children's Hospital, San Diego, CA 92123, USA.
FAU - Burns, Jane C
AU  - Burns JC
AD  - University of California San Diego, School of Medicine, Department of Pediatrics, 
      La Jolla, CA 92093-0641, USA.
AD  - Rady Children's Hospital, San Diego, CA 92123, USA.
FAU - Franco, Alessandra
AU  - Franco A
AUID- ORCID: 0000-0002-4840-8182
AD  - University of California San Diego, School of Medicine, Department of Pediatrics, 
      La Jolla, CA 92093-0641, USA.
LA  - eng
GR  - P30 AR073761/AR/NIAMS NIH HHS/United States
GR  - R01 AI143586/AI/NIAID NIH HHS/United States
GR  - R01 HL140898/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Adult
MH  - Anti-Inflammatory Agents/therapeutic use
MH  - Child
MH  - Dendritic Cells
MH  - Humans
MH  - *Immunoglobulins, Intravenous/pharmacology/therapeutic use
MH  - Interleukin-10
MH  - *Mucocutaneous Lymph Node Syndrome
MH  - T-Lymphocytes, Regulatory
PMC - PMC9226148
OTO - NOTNLM
OT  - Fcgamma receptors
OT  - IgG
OT  - natural regulatory T cells
OT  - tolerogenic myeloid dendritic cells
EDAT- 2022/05/11 06:00
MHDA- 2022/06/28 06:00
PMCR- 2022/05/10
CRDT- 2022/05/10 14:32
PHST- 2022/01/25 00:00 [received]
PHST- 2022/03/28 00:00 [revised]
PHST- 2022/05/04 00:00 [accepted]
PHST- 2022/05/11 06:00 [pubmed]
PHST- 2022/06/28 06:00 [medline]
PHST- 2022/05/10 14:32 [entrez]
PHST- 2022/05/10 00:00 [pmc-release]
AID - 6583428 [pii]
AID - uxac046 [pii]
AID - 10.1093/cei/uxac046 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2022 Jun 23;208(3):361-371. doi: 10.1093/cei/uxac046.