PMID- 30653608
OWN - NLM
STAT- MEDLINE
DCOM- 20191029
LR  - 20200309
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 1
DP  - 2019
TI  - Strain specific maturation of Dendritic cells and production of IL-1beta controls 
      CD40-driven colitis.
PG  - e0210998
LID - 10.1371/journal.pone.0210998 [doi]
LID - e0210998
AB  - Intestinal integrity is maintained by balanced numbers of CD103+ Dendritic cells 
      (DCs), which generate peripherally induced regulatory T cells (iTregs). We have 
      developed a mouse model where DC-specific constitutive CD40 signals caused a 
      strong reduction of CD103+ DCs in the lamina propria (LP) and intestinal lymph 
      nodes (LN). As a consequence, also iTregs were strongly reduced and transgenic 
      mice on the C57Bl/6-background (B6) developed fatal colitis. Here we describe 
      that transgenic mice on a pure Balb/c-background (B/c) do not show any 
      pathologies, while transgenic C57Bl/6 x Balb/c (F1) mice develop weak colon 
      inflammation, without fatal colitis. This graded pathology correlated with the 
      effects of CD40-signalling on DCs in each background, with striking loss of 
      CD103+ DCs in B6, but reduced in F1 and diminished in B/c background. We further 
      show direct correlation of CD103+ DC-numbers with numbers of iTregs, the 
      frequencies of which behave correspondingly. Striking effects on B6-DCs reflected 
      robust loss of surface MHCII, known to be crucial for iTreg induction. 
      Furthermore, elevated levels of IL-23 together with IL-1, found only in B6 mice, 
      support generation of intestinal IFN-gamma+IL-17+ Th17 cells and IFN-gamma+ Th1 cells, 
      responsible for onset of disease. Together, this demonstrates a novel aspect of 
      colitis-control, depending on genetic background. Moreover, strain-specific 
      environmental sensing might alter the CD103+ DC/iTreg-axis to tip intestinal 
      homeostatic balance to pathology.
FAU - Ogrinc Wagner, Ana
AU  - Ogrinc Wagner A
AD  - Institute for Immunology, Faculty of Medicine, Ludwig-Maximilians-Universitat 
      Munchen, Planegg-Martinsried, Germany.
FAU - Friedrich, Verena
AU  - Friedrich V
AD  - Institute for Immunology, Faculty of Medicine, Ludwig-Maximilians-Universitat 
      Munchen, Planegg-Martinsried, Germany.
FAU - Barthels, Christian
AU  - Barthels C
AD  - Institute for Immunology, Faculty of Medicine, Ludwig-Maximilians-Universitat 
      Munchen, Planegg-Martinsried, Germany.
FAU - Marconi, Peggy
AU  - Marconi P
AD  - Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 
      Ferrara, Italy.
FAU - Blutke, Andreas
AU  - Blutke A
AD  - Research Unit Analytical Pathology, Helmholtz Zentrum Munchen, Neuherberg, 
      Germany.
FAU - Brombacher, Frank
AU  - Brombacher F
AUID- ORCID: 0000-0001-8881-6781
AD  - Division of Immunology, University of Cape Town & South African Medical Research 
      Council, Cape Town, South Africa.
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      component, South Africa.
FAU - Brocker, Thomas
AU  - Brocker T
AUID- ORCID: 0000-0001-7060-5433
AD  - Institute for Immunology, Faculty of Medicine, Ludwig-Maximilians-Universitat 
      Munchen, Planegg-Martinsried, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190117
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, CD)
RN  - 0 (CD40 Antigens)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Interleukin-1beta)
RN  - 0 (alpha E integrins)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - CD40 Antigens/genetics/*metabolism
MH  - Colitis/genetics/*immunology/*pathology
MH  - Dendritic Cells/classification/*immunology/*pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Integrin alpha Chains/metabolism
MH  - Interleukin-1beta/*biosynthesis
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Signal Transduction/immunology
MH  - Species Specificity
MH  - T-Lymphocytes, Regulatory/classification/immunology/pathology
MH  - Th1 Cells/immunology/pathology
MH  - Th17 Cells/immunology/pathology
PMC - PMC6336277
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/01/18 06:00
MHDA- 2019/10/30 06:00
PMCR- 2019/01/17
CRDT- 2019/01/18 06:00
PHST- 2018/09/17 00:00 [received]
PHST- 2019/01/04 00:00 [accepted]
PHST- 2019/01/18 06:00 [entrez]
PHST- 2019/01/18 06:00 [pubmed]
PHST- 2019/10/30 06:00 [medline]
PHST- 2019/01/17 00:00 [pmc-release]
AID - PONE-D-18-27003 [pii]
AID - 10.1371/journal.pone.0210998 [doi]
PST - epublish
SO  - PLoS One. 2019 Jan 17;14(1):e0210998. doi: 10.1371/journal.pone.0210998. 
      eCollection 2019.