In:
The Journal of Immunology, The American Association of Immunologists, Vol. 192, No. 1_Supplement ( 2014-05-01), p. 68.14-68.14
Abstract:
Background: Dendritic cells (DC) and macrophages (Mφ) mediate intestinal immune tolerance. Recent evidence suggests intestinal CD103+CD11b- DC are involved in generation of regulatory T cells (T-reg), with CD103+CD11b+ DC stimulating Th17 cell differentiation. Information regarding gut DC function during inflammation is scarce. Methods: We compared murine and human gut DC and Mφ in the steady state and during intestinal inflammation, by flow cytometry. Results: Proportions of CD103-CD64+ Mφ were enhanced in the inflamed IL-10 knockout (KO) murine colon compared to WT, alongside a loss of CD103+CD11b- DC. Proportions of CD4+FoxP3+ T-reg were reduced in the inflamed IL-10 KO colon, with enhanced production of IL-17A and TNFα by T cells but a loss of regulatory TGFβ production by CD103+ DC. Proportions of CD103-CD64+ Mφ were also enhanced in the human Crohn’s disease colon compared to non-inflamed control tissue (diverticulitis), alongside a loss of CD103+ DC. CD103 was co-expressed with either CD141 or CD1c on human intestinal DC, corresponding to CD103+CD11b- and CD103+CD11b+ murine DC respectively. Proportions of all CD103+ gut DC subsets were reduced in human Crohn’s disease. Conclusions: Lack of IL-10 may skew DC and Mφ differentiation in the gut, leading to loss of DC able to generate T-reg. Further experiments will determine the ability of intestinal DC and Mφ subsets to stimulate specific T cell responses in vitro and the roles of IL-10 and TGFβ during this process.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.192.Supp.68.14
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2014
detail.hit.zdb_id:
1475085-5