PMID- 32480433
OWN - NLM
STAT- MEDLINE
DCOM- 20210209
LR  - 20210325
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Linking)
VI  - 108
IP  - 5
DP  - 2020 Nov
TI  - Human neutrophils activated by TLR8 agonists, with or without IFNgamma, synthesize 
      and release EBI3, but not IL-12, IL-27, IL-35, or IL-39.
PG  - 1515-1526
LID - 10.1002/JLB.3MA0520-054R [doi]
AB  - The IL-12 family of cytokines plays crucial functions in innate and adaptive 
      immunity. These cytokines include heterodimers sharing distinct alpha (IL-12A, 
      IL-23A, and IL-27A) with two beta (IL-12B and Epstein-Barr virus induced gene 3 
      [EBI3]) chains, respectively, IL-12 (IL-12B plus IL-12A) and IL-23 (IL-12B plus 
      IL-23A) sharing IL-12B, IL-27 (EBI3 plus IL-27A), IL-35 (EBI3 plus IL-12A), and 
      IL-39 (EBI3 plus IL-23A) sharing EBI3. In this context, we have recently reported 
      that highly pure neutrophils incubated with TLR8 agonists produce functional 
      IL-23. Previously, we showed that neutrophils incubated with LPS plus IFNgamma for 
      20 h produce IL-12. Herein, we investigated whether highly pure, TLR8-activated, 
      neutrophils produce EBI3, and in turn IL-27, IL-35, and IL-39, the IL-12 members 
      containing it. We report that neutrophils incubated with TLR8 ligands, TNFalpha and, 
      to a lesser extent, LPS, produce and release remarkable amounts of EBI3, but not 
      IL-27A, consequently excluding the possibility for an IL-27 production. We also 
      report a series of unsuccessful experiments performed to investigate whether 
      neutrophil-derived EBI3 associates with IL-23A to form IL-39. Furthermore, we 
      show that neutrophils incubated with IFNgamma in combination with either TLR8 or TLR4 
      ligands express/produce neither IL-12, nor IL-35, due to the inability of IFNgamma, 
      contrary to previous findings, to activate IL12A transcription. Even IL-27 was 
      undetectable in supernatants harvested from IFNgamma plus R848-treated neutrophils, 
      although they were found to accumulate IL27A transcripts. Finally, by 
      immunohistochemistry experiments, EBI3-positive neutrophils were found in 
      discrete pathologies only, including diverticulitis, cholecystitis, Gorham 
      disease, and Bartonella Henselae infection, implying a specific role of 
      neutrophil-derived EBI3 in vivo.
CI  - (c)2020 Society for Leukocyte Biology.
FAU - Cassatella, Marco A
AU  - Cassatella MA
AUID- ORCID: 0000-0001-7824-1806
AD  - Department of Medicine, Section of General Pathology, University of Verona, 
      Verona, Italy.
FAU - Gardiman, Elisa
AU  - Gardiman E
AD  - Department of Medicine, Section of General Pathology, University of Verona, 
      Verona, Italy.
FAU - Arruda-Silva, Fabio
AU  - Arruda-Silva F
AD  - Department of Medicine, Section of General Pathology, University of Verona, 
      Verona, Italy.
FAU - Bianchetto-Aguilera, Francisco
AU  - Bianchetto-Aguilera F
AD  - Department of Medicine, Section of General Pathology, University of Verona, 
      Verona, Italy.
FAU - Gasperini, Sara
AU  - Gasperini S
AD  - Department of Medicine, Section of General Pathology, University of Verona, 
      Verona, Italy.
FAU - Bugatti, Mattia
AU  - Bugatti M
AD  - Department of Molecular and Translational Medicine, Section of Pathology, 
      University of Brescia, Brescia, Italy.
FAU - Vermi, William
AU  - Vermi W
AD  - Department of Molecular and Translational Medicine, Section of Pathology, 
      University of Brescia, Brescia, Italy.
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      Saint Louis, Missouri, USA.
FAU - Larousserie, Frederique
AU  - Larousserie F
AD  - Sorbonne Universite, INSERM, CNRS, Centre d'Immunologie et des Maladies 
      Infectieuses, Paris, France.
AD  - Departement de Pathologie, Hopital Cochin, AP-HP, Universite de Paris, Paris, 
      France.
FAU - Devergne, Odile
AU  - Devergne O
AD  - Sorbonne Universite, INSERM, CNRS, Centre d'Immunologie et des Maladies 
      Infectieuses, Paris, France.
FAU - Tamassia, Nicola
AU  - Tamassia N
AD  - Department of Medicine, Section of General Pathology, University of Verona, 
      Verona, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200601
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (EBI3 protein, human)
RN  - 0 (IFNG protein, human)
RN  - 0 (Imidazoles)
RN  - 0 (Interleukins)
RN  - 0 (MYDGF protein, human)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (TLR8 protein, human)
RN  - 0 (Toll-Like Receptor 8)
RN  - 0 (interleukin 39, human)
RN  - 0 (interleukin-35, human)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - V3DMU7PVXF (resiquimod)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Imidazoles/*pharmacology
MH  - Interferon-gamma/immunology
MH  - Interleukin-12/immunology
MH  - Interleukins/immunology
MH  - Mice
MH  - Minor Histocompatibility Antigens/immunology
MH  - Neutrophils/*immunology/pathology
MH  - Toll-Like Receptor 8/*agonists/immunology
OTO - NOTNLM
OT  - EBI3
OT  - IL-12
OT  - IL-27
OT  - IL-35
OT  - Neutrophils
OT  - TLR8
OT  - TNFalpha
EDAT- 2020/06/02 06:00
MHDA- 2021/02/10 06:00
CRDT- 2020/06/02 06:00
PHST- 2020/02/16 00:00 [received]
PHST- 2020/05/08 00:00 [accepted]
PHST- 2020/06/02 06:00 [pubmed]
PHST- 2021/02/10 06:00 [medline]
PHST- 2020/06/02 06:00 [entrez]
AID - 10.1002/JLB.3MA0520-054R [doi]
PST - ppublish
SO  - J Leukoc Biol. 2020 Nov;108(5):1515-1526. doi: 10.1002/JLB.3MA0520-054R. Epub 
      2020 Jun 1.