Transforming growth factor-beta 1 (TGF-β1) down-regulates IgA Fc-receptor (CD89) expression on human monocytes

Triggering receptor expressed on myeloid cells (TREM)-1 is a cell surface molecule on neutrophils and monocytes/macrophages implicated in the amplification of inflammatory responses by enhancing degranulation and secretion of proinflammatory mediators. Macrophages play an important role in the intestinal mucosal immune system, because they are preferentially localized in the subepithelial region. Despite the presence of enormous numbers of bacteria in the colonic mucosa and the close proximity between mucosal macrophages and luminal bacteria, the intestinal mucosa normally displays minimal signs of inflammation. In this study, we show that the resident macrophage population in normal human small and large intestine contains only few TREM-1-expressing macrophages (<10%), whereas the overwhelming majority of monocytes (>90%) and macrophages from lymph nodes or tonsils (>80%) express TREM-1 on the cell surface. These findings were confirmed by FACS analysis and immunostainings of frozen tissue sections. The differential expression of TREM-1 greatly affects the functional capacities of monocytes and tissue macrophages. Although monocytes and macrophages from spleen, lymph nodes, or tonsils show a substantial increase in oxidative burst after TREM-1 cross-linking, no effect is seen in intestinal macrophages. Intriguingly, in contrast to monocytes, intestinal macrophages fail to up-regulate TREM-1 in response to TNF. This refractory state may be induced in intestinal macrophages by the local presence of IL-10 and TGF-β, because these two immunoregulatory cytokines synergistically down-regulate TREM-1 expression on monocytes in vitro. The absence of TREM-1 expression on lamina propria macrophages is likely to prevent excessive inflammatory reactions, and thus, excessive tissue damage in the intestine.

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“…4). A similar synergistic effect of IL-10 and TGF-␤ has been previously noted for down-modulation of CD89 on monocytes (27,32).…”

Section: Discussionsupporting

confidence: 80%

Macrophages Expressing Triggering Receptor Expressed on Myeloid Cells-1 Are Underrepresented in the Human Intestine

Schenk

Bouchon

Birrer

et al. 2005

The Journal of Immunology

106

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“…Monocyte-derived interstitial-type DC (cultured in the absence of TGF-␤1) express CD89 albeit at lower levels than monocytes, while CD89 expression appears to be further down-regulated in monocyte-derived LC-type DC that are obtained by addition of TGF-␤1. Furthermore, TGF-␤1 has been shown to down-regulate IgA Fc-receptor (CD89) expression on human monocytes (29). Therefore, it is likely that TGF-␤1 is responsible for the downregulation of CD89 on LC in human skin and gingival mucosa.…”

Section: Discussionmentioning

confidence: 99%

A Subset of Human Dendritic Cells Expresses IgA Fc Receptor (CD89), Which Mediates Internalization and Activation Upon Cross-Linking by IgA Complexes

Geissmann

Launay

Pasquier

et al. 2001

The Journal of Immunology

135

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Immature dendritic cells (DC) sample Ags within nonlymphoid tissues and acquire exogenous proteins/pathogens via scavenger receptors or Ig FcR such as FcγR and FcεR. IgA is present in a significant proportion among serum Ig and is the main isotype in mucosae, where DC are numerous. We found that a functional FcαR (CD89) was expressed in situ and in vitro on interstitial-type DC but not on Langerhans cell-type DC. Interstitial-type DC expressed CD89 as a 50- to 75-kDa glycoprotein with a 32-kDa protein core, which was down-regulated upon addition of TGF-β1. DC, FcαR specifically, bound IgA1 and IgA2. Cross-linking of CD89 on DC triggered endocytosis in time-dependent manner. In addition, internalization of polymeric IgA complexes induced the production of IL-10 and DC activation, as reflected by up-regulation of CD86 costimulatory molecules, class II MHC expression, and increased allostimulatory activity. Therefore, interstitial-type DC may use FcαR-mediated Ag sampling in the subepithelium to check tissue integrity while Langerhans cells inside epithelial layers may neglect IgA immune complexes.

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“…Alternatively, the absence of CD14 and CD89 on lamina propria macrophages could have occurred in vivo in response to locally produced cytokines, such as IL-4 and IL-13, which down-regulate CD14 expression (22,23), or IFN-␥ and TGF-␤1, which downregulate CD89 (24,25). To address this possibility, elutriated blood monocytes were analyzed for CD14 and CD89 expression before and after a 24-h exposure to mucosal cell-conditioned medium (dilution 1/2) prepared from 24-h cultures of purified jejunal epithelial cells (1 ϫ 10 7 cells/ml), lamina propria mononuclear cells (1 ϫ 10 7 cells/ml), and the lamina propria stroma after removal of the mononuclear cells (wet weight, 1 g/ml).…”

Section: Lamina Propria Macrophages Do Not Express Surface Cd14 or Cd89mentioning

confidence: 99%

Intestinal Macrophages Lack CD14 and CD89 and Consequently Are Down-Regulated for LPS- and IgA-Mediated Activities

Smith

Smythies

Mosteller-Barnum

et al. 2001

The Journal of Immunology

294

242

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The intestinal mucosa normally displays minimal inflammation despite the close proximity between mucosal macrophages and lumenal bacteria. Macrophages interact with bacteria and their products through CD14, a surface receptor involved in the response to LPS, and CD89, the receptor for IgA (FcαR). Here we show that resident macrophages isolated from normal human intestine lack CD14 and CD89. The absence of CD14 and CD89 was not due to the isolation procedure or mucosal cell products, but was evident at the transcriptional level, as the macrophages expressed neither CD14- nor CD89-specific mRNAs, but did express Toll-like receptor 2 and 4 transcripts. Consistent with their CD14− phenotype, lamina propria macrophages displayed markedly reduced LPS-induced cytokine production and LPS-enhanced phagocytosis. In addition, IgA-enhanced phagocytosis was sharply reduced in lamina propria macrophages. Thus, the absence of CD14 and CD89 on resident intestinal macrophages, due to down-regulated gene transcription, causes down-modulated LPS- and IgA-mediated functions and probably contributes to the low level of inflammation in normal human intestinal mucosa.

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Transforming growth factor-beta 1 (TGF-β1) down-regulates IgA Fc-receptor (CD89) expression on human monocytes

Cited by 43 publications

References 27 publications

Macrophages Expressing Triggering Receptor Expressed on Myeloid Cells-1 Are Underrepresented in the Human Intestine

Macrophages Expressing Triggering Receptor Expressed on Myeloid Cells-1 Are Underrepresented in the Human Intestine

A Subset of Human Dendritic Cells Expresses IgA Fc Receptor (CD89), Which Mediates Internalization and Activation Upon Cross-Linking by IgA Complexes

Intestinal Macrophages Lack CD14 and CD89 and Consequently Are Down-Regulated for LPS- and IgA-Mediated Activities

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