PMID- 19632232
OWN - NLM
STAT- MEDLINE
DCOM- 20091203
LR  - 20220330
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Linking)
VI  - 137
IP  - 5
DP  - 2009 Nov
TI  - Th1/Th17 immune response is induced by mesenteric lymph node dendritic cells in 
      Crohn's disease.
PG  - 1736-45
LID - 10.1053/j.gastro.2009.07.049 [doi]
AB  - BACKGROUND & AIMS: Dendritic cells (DCs) possess the most potent ability to 
      induce acquired immunity. However, their involvement in the pathogenesis of 
      Crohn's disease (CD) has not yet been determined. We aimed to establish the 
      immune status of mesenteric lymph nodes, the major gut-associated lymphoid 
      tissue, and isolated DCs and determine their involvement in the pathogenesis of 
      CD. METHODS: CD4(+) T cells and DCs were isolated from mesenteric lymph nodes of 
      CD, ulcerative colitis, and normal control. The immune status of CD4(+) T cells 
      was analyzed by cytokine production and transcriptional profile. Surface 
      phenotype of DCs was analyzed by flow cytometry. Cytokine production by myeloid 
      DCs was analyzed by real-time polymerase chain reaction and exogenous bacterial 
      stimulation. Immune stimulating activity of DCs was determined by mixed 
      lymphocyte reaction. RESULTS: In CD, mesenteric lymph node CD4(+) T cells 
      produced higher amounts of interferon-gamma and interleukin (IL)-17 compared with 
      ulcerative colitis and normal control, and this was dictated by increased T-bet 
      and retinoic acid-related orphan receptor-gamma expression. Three subtypes of 
      DCs, myeloid DC, plasmacytoid DC, and mature DC, were identified in all groups. 
      When stimulated with exogenous bacterial derivative, myeloid DCs from CD produced 
      a higher amount of IL-23 and a lower amount of IL-10. Myeloid DCs from CD induced 
      stronger T helper cell (Th)1 immune response in mixed lymphocyte reaction 
      compared with those from ulcerative colitis and normal control. CONCLUSIONS: Our 
      findings revealed that mesenteric lymph node is the key pathogenic location of CD 
      elicited by the unique cytokine milieu produced by DCs leading to a dysregulated 
      Th1/Th17 immune response.
FAU - Sakuraba, Atsushi
AU  - Sakuraba A
AD  - Division of Gastroenterology, Department of Internal Medicine, Keio University 
      School of Medicine, Tokyo, Japan.
FAU - Sato, Toshiro
AU  - Sato T
FAU - Kamada, Nobuhiko
AU  - Kamada N
FAU - Kitazume, Mina
AU  - Kitazume M
FAU - Sugita, Akira
AU  - Sugita A
FAU - Hibi, Toshifumi
AU  - Hibi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090724
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Interleukin-17)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
CIN - Gastroenterology. 2009 Nov;137(5):1566-70. PMID: 19789081
MH  - Case-Control Studies
MH  - Crohn Disease/*immunology/metabolism/*pathology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Humans
MH  - Immunity, Cellular/physiology
MH  - Interferon-gamma/metabolism
MH  - Interleukin-17/metabolism
MH  - Lymph Nodes/immunology/metabolism/*pathology
MH  - Mesentery
MH  - Th1 Cells/*physiology
EDAT- 2009/07/28 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/07/28 09:00
PHST- 2008/10/22 00:00 [received]
PHST- 2009/06/24 00:00 [revised]
PHST- 2009/07/16 00:00 [accepted]
PHST- 2009/07/28 09:00 [entrez]
PHST- 2009/07/28 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - S0016-5085(09)01248-7 [pii]
AID - 10.1053/j.gastro.2009.07.049 [doi]
PST - ppublish
SO  - Gastroenterology. 2009 Nov;137(5):1736-45. doi: 10.1053/j.gastro.2009.07.049. 
      Epub 2009 Jul 24.