PMID- 21135170
OWN - NLM
STAT- MEDLINE
DCOM- 20110127
LR  - 20131121
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 186
IP  - 1
DP  - 2011 Jan 1
TI  - Glucocorticosteroids modify Langerhans cells to produce TGF-beta and expand 
      regulatory T cells.
PG  - 103-12
LID - 10.4049/jimmunol.1002485 [doi]
AB  - Although glucocorticosteroids (GCSs) have been used for many decades in 
      transplantation and (auto)inflammatory diseases, the exact mechanisms responsible 
      for their immunosuppressive properties are not fully understood. The purpose of 
      this study was to characterize the effects of oral GCSs on the cutaneous immune 
      response. We analyzed, by immunofluorescence staining and quantitative RT-PCR, 
      residual skin biopsy material from a clinical study in which we had used oral GCS 
      as positive control for determining the effects of candidate anti-inflammatory 
      compounds on epicutaneous patch tests of Ni-allergic patients. Expectedly, oral 
      GCS treatment led to a reduction of clinical symptoms and infiltrating 
      leukocytes. Notably, we observed increased numbers of dermal FOXP3(+)CD25(+) T 
      cells and epidermal Langerhans cells (LCs) that were associated with upregulated 
      mRNA expression of TGF-beta in lesions of GCS-treated Ni-allergic patients. To 
      investigate this phenomenon further, we exposed purified LCs to GCS. They 
      exhibited, in contrast to GCS-nonexposed LCs, 1) a more immature phenotype, 2) 
      higher intracellular amounts of TGF-beta, and 3) increased receptor activator for 
      NF-kappaB expression, conditions that reportedly favor the expansion of regulatory T 
      cells (Tregs). Indeed, we observed an enhancement of functionally suppressive 
      FOXP3(+) T cells when CD3(+) cells were incubated with GCS-pretreated LCs. The 
      expansion of Tregs was inhibited by TGF-beta blockage alone, and their suppressive 
      activity was neutralized by a combination of anti-TGF-beta and anti-IL-10 Abs. Our 
      data show that systemically applied GCSs endow LCs with Treg-promoting properties 
      and thus shed new light on the mechanisms of GCS-mediated immunosuppression.
FAU - Stary, Georg
AU  - Stary G
AD  - Division of Immunology, Allergy and Infectious Diseases, Department of 
      Dermatology, Medical University of Vienna, 1090 Vienna, Austria. 
      georg.stary@meduniwien.ac.at
FAU - Klein, Irene
AU  - Klein I
FAU - Bauer, Wolfgang
AU  - Bauer W
FAU - Koszik, Frieder
AU  - Koszik F
FAU - Reininger, Barbel
AU  - Reininger B
FAU - Kohlhofer, Sabine
AU  - Kohlhofer S
FAU - Gruber, Kristina
AU  - Gruber K
FAU - Skvara, Hans
AU  - Skvara H
FAU - Jung, Thomas
AU  - Jung T
FAU - Stingl, Georg
AU  - Stingl G
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20101206
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Allergens)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 7OV03QG267 (Nickel)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Allergens/administration & dosage/immunology
MH  - Cell Differentiation/drug effects/*immunology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Immunophenotyping
MH  - Inflammation Mediators/administration & dosage
MH  - Langerhans Cells/drug effects/*immunology/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Nickel/administration & dosage/immunology
MH  - *Patch Tests/methods
MH  - Prednisone/administration & dosage/*pharmacology
MH  - Reproducibility of Results
MH  - T-Lymphocytes, Regulatory/cytology/drug effects/*immunology
MH  - Transforming Growth Factor beta/*biosynthesis
MH  - Young Adult
EDAT- 2010/12/08 06:00
MHDA- 2011/01/29 06:00
CRDT- 2010/12/08 06:00
PHST- 2010/12/08 06:00 [entrez]
PHST- 2010/12/08 06:00 [pubmed]
PHST- 2011/01/29 06:00 [medline]
AID - jimmunol.1002485 [pii]
AID - 10.4049/jimmunol.1002485 [doi]
PST - ppublish
SO  - J Immunol. 2011 Jan 1;186(1):103-12. doi: 10.4049/jimmunol.1002485. Epub 2010 Dec 
      6.