Z Gastroenterol 2018; 56(05): e6
DOI: 10.1055/s-0038-1648568
Kategorie: Presidential Poster
Georg Thieme Verlag KG Stuttgart · New York

CD1a expressing monocytes as sensors and mediators of inflammation in ulcerative colitis

O Al-amodi
1   Department of General- Visceral-, Vascular- and Transplantation Surgery, Hospital of the LMU, München
,
H Jodeleit
2   Institute of Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich
,
F Beigel
3   Department of Medicine II-Grosshadern, Hospital of the LMU Munich
,
E Wolf
2   Institute of Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich
,
M Siebeck
1   Department of General- Visceral-, Vascular- and Transplantation Surgery, Hospital of the LMU, München
,
R Gropp
1   Department of General- Visceral-, Vascular- and Transplantation Surgery, Hospital of the LMU, München
› Author Affiliations
Further Information

Publication History

Publication Date:
03 May 2018 (online)

Also available at
 

Background:

CD1a presents self-lipids such as triacylglycerol (TAG) and phosphatidylcholine (PC) to the conventional CD4+ repertoire and thereby induces autoreactive T cells. CD1a expressing monocytes have been identified as a biological marker of ulcerative colitis (UC) and as an inflammatory marker in the NSG-UC mouse model which is based on NOD/scid IL2Rγnull (NSG) mice reconstituted with peripheral blood mononuclear cells (PBMC) from UC patients. In this study the function of CD1a expressing monocytes has been examined in vitro and in vivo. In addition, CD1a was evaluated as a potential therapeutic target for treatment of UC.

Methods:

Peripheral blood mononuclear cells (PBMC) from UC patients and non-UC donors were incubated with PC for 2 and 7 days and subjected to flow cytometric analysis. Proliferation was examined by CellTrace™ CFSE. Triacylglycerol (TAG) and cholesterol levels and frequencies of CD14+CD1a+ monocytes were determined in the NSG-UC mouse model in response to challenge with ethanol. NSG-UC mice were treated with anti-CD1a antibodies. Response to treatment was determined by clinical- and histological scores, flow cytometric analysis of human leucocytes from spleen and colon and expression levels of TGFß1, HGF, IFNγ and TARC.

Results:

Incubation of PBMC with PC resulted in an increase of frequencies of CD1a+ CD14+ monocytes at the expense of CCR2, CD86 and TSLPR expressing CD14+ monocytes. Analysis by CellTrace™ CFSE revealed a proliferation of CD1a expressing monocytes in response to PC. In addition, IFNγ levels increased whereas IL-10 levels decreased. CD1a+ CD14+ monocytes induced the activation of CD4+ T cells and differentiation of Th cells. This effect was reversed in the presence of anti CD1a antibodies. In vivo, TAG and cholesterol levels increased upon inflammation and correlated positively with CD14+ CD1a+ monocytes. NSG-UC mice benefitted from treatment with anti-CD1a antibodies as indicated by a reduced clinical and histological scores and reduced frequencies of CD1a+ CD14+ monocytes in the colon and spleen of mice.

Conclusion:

Data suggest that CD1a expressing monocytes act as sensors and mediators of inflammation in UC. CD1a is an attractive therapeutic target in UC.