PMID- 19234153
OWN - NLM
STAT- MEDLINE
DCOM- 20090421
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 182
IP  - 5
DP  - 2009 Mar 1
TI  - Amplification of autoimmune response through induction of dendritic cell 
      maturation in inflamed tissues.
PG  - 2590-600
LID - 10.4049/jimmunol.0803543 [doi]
AB  - Dendritic cells (DCs) are essential in T cell-mediated destruction of 
      insulin-producing beta cells in the islets of Langerhans in type 1 diabetes. In 
      this study, we investigated T cell induction of intra-islet DC maturation during 
      the progression of the disease in both autoimmune-prone NOD and resistant C57BL/6 
      mice. We demonstrated steady-state capture and retention of unprocessed beta 
      cell-derived proteins by semimature intra-islet DCs in both mouse strains. T 
      cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 
      expression and processing of captured Ag by resident DCs without inducing the 
      expression of the p40 subunit of IL-12/23. Some of the CD40(high) intra-islet DCs 
      up-regulated CCR7, and a small number of CD40(high) DCs bearing unprocessed islet 
      Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet 
      inflammation, demonstrating that T cell-mediated tissue inflammation augments 
      migration of mature resident DCs to draining lymph nodes. Our results identify an 
      amplification loop during the progression of autoimmune diabetes, in which 
      initial T cell infiltration leads to rapid maturation of intra-islet DCs, their 
      migration to lymph nodes, and expanded priming of more autoreactive T cells. 
      Therapeutic interventions that intercept this process may be effective at halting 
      the progression of type 1 diabetes.
FAU - Melli, Kristin
AU  - Melli K
AD  - Department of Surgery, University of California, San Francisco, CA 94143, USA.
FAU - Friedman, Rachel S
AU  - Friedman RS
FAU - Martin, Ashley E
AU  - Martin AE
FAU - Finger, Erik B
AU  - Finger EB
FAU - Miao, Gang
AU  - Miao G
FAU - Szot, Gregory L
AU  - Szot GL
FAU - Krummel, Matthew F
AU  - Krummel MF
FAU - Tang, Qizhi
AU  - Tang Q
LA  - eng
GR  - R37 AI046643/AI/NIAID NIH HHS/United States
GR  - R21 AI066097/AI/NIAID NIH HHS/United States
GR  - R37 AI46643/AI/NIAID NIH HHS/United States
GR  - R21 AI066097-02/AI/NIAID NIH HHS/United States
GR  - R21 AI66097/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (pancreatic and duodenal homeobox 1 protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/*immunology/metabolism/*pathology
MH  - Cell Differentiation/genetics/*immunology
MH  - Dendritic Cells/*immunology/metabolism/*pathology
MH  - Diabetes Mellitus, Type 1/immunology/metabolism/pathology
MH  - Female
MH  - Green Fluorescent Proteins/genetics
MH  - Homeodomain Proteins/physiology
MH  - Immunophenotyping
MH  - Inflammation/immunology/metabolism/pathology
MH  - Islets of Langerhans/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - T-Lymphocytes/immunology
MH  - Trans-Activators/physiology
PMC - PMC3057894
MID - NIHMS276365
COIS- Disclosures The authors have no financial conflict of interest.
EDAT- 2009/02/24 09:00
MHDA- 2009/04/22 09:00
PMCR- 2011/03/15
CRDT- 2009/02/24 09:00
PHST- 2009/02/24 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2009/04/22 09:00 [medline]
PHST- 2011/03/15 00:00 [pmc-release]
AID - 182/5/2590 [pii]
AID - 10.4049/jimmunol.0803543 [doi]
PST - ppublish
SO  - J Immunol. 2009 Mar 1;182(5):2590-600. doi: 10.4049/jimmunol.0803543.