PMID- 24554774
OWN - NLM
STAT- MEDLINE
DCOM- 20140515
LR  - 20220107
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 192
IP  - 6
DP  - 2014 Mar 15
TI  - IL-27 in human secondary lymphoid organs attracts myeloid dendritic cells and 
      impairs HLA class I-restricted antigen presentation.
PG  - 2634-42
LID - 10.4049/jimmunol.1302656 [doi]
AB  - Different cytokines play crucial roles in inflammation and in polarizing immune 
      responses, including IL-27 that exerts pro- and anti-inflammatory functions. 
      Although the activity of IL-27 is well characterized in murine immune cells, only 
      limited information is available regarding the natural cellular sources of IL-27 
      in humans and its effects on human immune cells. Dendritic cells (DCs) are the 
      most potent professional APCs that in the immature state are positioned 
      throughout peripheral tissues by acting as sentinels, sensing the presence of 
      Ags. Activated DCs migrate into the lymph nodes and direct Ag-specific T cell 
      responses, thus acting as key players in both adaptive and innate immunity. In 
      this study we asked whether IL-27 is produced by human secondary lymphoid organs 
      and what is its functional role on human DCs. To our knowledge, we provide the 
      first evidence that 1) in lymph nodes, macrophages are the major source for 
      IL-27; 2) immature and mature human DCs express functional IL-27R; 3) IL-27 
      exerts immunosuppressive activity by crippling the Ag processing machinery in 
      immature DCs under steady-state conditions and after pulsing with a viral Ag; and 
      4) IL-27 is chemotactic for human DCs. Our findings highlight novel mechanisms 
      underlying the immunosuppressive activity of IL-27, suggesting that this cytokine 
      may function as a homeostatic cytokine in secondary lymphoid organs by limiting 
      duration and/or intensity of ongoing adaptive immune responses. The results 
      presented in this study pave the way to future studies aimed at investigating 
      whether dysregulation of IL-27 expression and function may be involved in 
      pathogenesis of autoimmune disease and cancer.
FAU - Morandi, Fabio
AU  - Morandi F
AD  - Laboratorio di Oncologia, Istituto Giannina Gaslini, 16147 Genoa, Italy;
FAU - Di Carlo, Emma
AU  - Di Carlo E
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - Petretto, Andrea
AU  - Petretto A
FAU - Pistoia, Vito
AU  - Pistoia V
FAU - Airoldi, Irma
AU  - Airoldi I
LA  - eng
GR  - R01 CA110249/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140219
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD11c Antigen)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (IL27RA protein, human)
RN  - 0 (Interleukin-27)
RN  - 0 (Receptors, Interleukin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - O5GA75RST7 (EBV-encoded nuclear antigen 1)
SB  - IM
MH  - Antigen Presentation/*immunology
MH  - Antigens, CD/immunology/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/immunology/metabolism
MH  - CD11c Antigen/immunology/metabolism
MH  - Cell Movement/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/metabolism
MH  - Epstein-Barr Virus Nuclear Antigens/immunology/metabolism
MH  - Flow Cytometry
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Immune System/*immunology/metabolism
MH  - Immunohistochemistry
MH  - Interferon-gamma/immunology/metabolism
MH  - Interleukin-27/*immunology/metabolism
MH  - Lymph Nodes/immunology/metabolism
MH  - Macrophages/immunology/metabolism
MH  - Microscopy, Confocal
MH  - Myeloid Cells/immunology/metabolism
MH  - Receptors, Interleukin/immunology/metabolism
MH  - T-Lymphocytes/immunology/metabolism
PMC - PMC8728891
MID - NIHMS1764809
COIS- Disclosures The authors have no financial conflicts of interest.
EDAT- 2014/02/21 06:00
MHDA- 2014/05/16 06:00
PMCR- 2022/01/05
CRDT- 2014/02/21 06:00
PHST- 2014/02/21 06:00 [entrez]
PHST- 2014/02/21 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
PHST- 2022/01/05 00:00 [pmc-release]
AID - jimmunol.1302656 [pii]
AID - 10.4049/jimmunol.1302656 [doi]
PST - ppublish
SO  - J Immunol. 2014 Mar 15;192(6):2634-42. doi: 10.4049/jimmunol.1302656. Epub 2014 
      Feb 19.