PMID- 11375417
OWN - NLM
STAT- MEDLINE
DCOM- 20010628
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 107
IP  - 10
DP  - 2001 May
TI  - Dendritic cells genetically engineered to express IL-4 inhibit murine 
      collagen-induced arthritis.
PG  - 1275-84
AB  - Dendritic cells (DCs) are specialized antigen-presenting cells that migrate from 
      the periphery to lymphoid tissues, where they activate and regulate T cells. 
      Genetic modification of DCs to express immunoregulatory molecules would provide a 
      new immunotherapeutic strategy for autoimmune and other diseases. We have 
      engineered bone marrow-derived DCs that express IL-4 and tested the ability of 
      these cells to control murine collagen-induced arthritis (CIA), a model for 
      rheumatoid arthritis in which Th1 cells play a critical role. IL-4-transduced DCs 
      inhibited Th1 responses to collagen type II in vitro. A single injection of 
      IL-4-transduced DCs reduced the incidence and severity of CIA and suppressed 
      established Th1 responses and associated humoral responses, despite only 
      transient persistence of injected DCs in the spleen. In contrast, control DCs and 
      IL-4-transduced T cells or fibroblastic cells failed to alter the course of the 
      disease. The functional effects correlated well with the differential efficiency 
      of DC migration from various sites of injection to lymphoid organs, especially 
      the spleen. The ability of splenic T cells to produce IL-4 in response to 
      anti-CD3 was enhanced after the administration of IL-4-transduced DCS: These 
      results support the feasibility of using genetically modified DCs for the 
      treatment of autoimmune disease.
FAU - Morita, Y
AU  - Morita Y
AD  - Division of Rheumatology, Department of Internal Medicine, University of 
      Michigan, Ann Arbor, Michigan 48109, USA.
FAU - Yang, J
AU  - Yang J
FAU - Gupta, R
AU  - Gupta R
FAU - Shimizu, K
AU  - Shimizu K
FAU - Shelden, E A
AU  - Shelden EA
FAU - Endres, J
AU  - Endres J
FAU - Mule, J J
AU  - Mule JJ
FAU - McDonagh, K T
AU  - McDonagh KT
FAU - Fox, D A
AU  - Fox DA
LA  - eng
GR  - R01 AR038477/AR/NIAMS NIH HHS/United States
GR  - AR38477/AR/NIAMS NIH HHS/United States
GR  - DK02349/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 207137-56-2 (Interleukin-4)
RN  - 9007-34-5 (Collagen)
SB  - IM
CIN - J Clin Invest. 2001 Jun;107(11):1353. PMID: 11390415
MH  - Animals
MH  - Arthritis, Rheumatoid/chemically induced/*therapy
MH  - Bone Marrow Transplantation
MH  - Cell Movement
MH  - Collagen
MH  - Dendritic Cells/*transplantation
MH  - Genetic Engineering
MH  - Immunotherapy/methods
MH  - Interleukin-4/*biosynthesis/*genetics
MH  - Mice
MH  - Retroviridae/genetics
MH  - Spleen/cytology/immunology
PMC - PMC209294
EDAT- 2001/05/26 10:00
MHDA- 2001/06/29 10:01
PMCR- 2001/05/15
CRDT- 2001/05/26 10:00
PHST- 2001/05/26 10:00 [pubmed]
PHST- 2001/06/29 10:01 [medline]
PHST- 2001/05/26 10:00 [entrez]
PHST- 2001/05/15 00:00 [pmc-release]
AID - 11490 [pii]
AID - 10.1172/JCI11490 [doi]
PST - ppublish
SO  - J Clin Invest. 2001 May;107(10):1275-84. doi: 10.1172/JCI11490.