T-cell co-stimulatory molecules are upregulated on intestinal macrophages from inflammatory bowel disease mucosa

Rogler, Gerhard; Hausmann, Martin; Spöttl, T.; Vogl, Daniela; Aschenbrenner, E; Andus, Tilo; Falk, Werner; Schölmerich, Jürgen; Groß, Volker

doi:10.1097/00042737-199910000-00006

Cited by 48 publications

(48 citation statements)

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“…In contrast to the abundant expression of B7-H1, B7-DC expression in the inflamed lung was limited, especially on lung macrophages. Consistent with previous reports (6,(41)(42)(43), we observed reduced expression of CD86 and B7-DC on lung macrophages compared with other peripheral tissues. Similar findings were reported in the CNS of mice with experimental autoimmune encephalomyelitis (44).…”

Section: Discussionsupporting

confidence: 93%

B7-DC Regulates Asthmatic Response by an IFN-γ-Dependent Mechanism

Matsumoto

Inoue

Nakano

et al. 2004

The Journal of Immunology

134

112

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B7-H1 (PD-L1) and B7-DC (PD-L2) are the ligands for programmed death-1 (PD-1), which is a member of the CD28/CTLA-4 family and has been implicated in peripheral tolerance. We investigated the roles of B7-H1 and B7-DC in a murine OVA-induced allergic asthma model. B7-H1 was constitutively expressed on dendritic cells, macrophages, B cells, and T cells in the lungs of naive mice, and its expression could be dramatically increased after allergen challenge. In contrast, B7-DC expression was scarcely expressed on dendritic cells in naive mice, but was up-regulated after allergen challenge, although the up-regulation of B7-DC expression on macrophages was minimal. Treatment of mice with anti-B7-DC mAb at the time of allergen challenge, but not at the time of sensitization, significantly increased their airway hyper-reactivity and eosinophilia. Such treatment also resulted in the increased production of IL-5 and IL-13, and decreased IFN-γ production in the lungs and draining lymph node cells. These changes were diminished when mice were depleted of IFN-γ by anti-IFN-γ mAb pretreatment. Interestingly, treatment with anti-B7-H1 or anti-PD-1 mAb did not significantly affect the asthmatic response. These results suggest a unique role for B7-DC in the regulation of asthmatic response through an IFN-γ-dependent, but PD-1-independent, mechanism.

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Section: Discussionsupporting

confidence: 93%

B7-DC Regulates Asthmatic Response by an IFN-γ-Dependent Mechanism

Matsumoto

Inoue

Nakano

et al. 2004

The Journal of Immunology

134

112

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“…In addition, Meijssen et al reported expression of CD14 mRNA in intestinal epithelial cells of IL-2 Ϫ/Ϫ mice, which develop inflammatory bowel disease resembling human ulcerative colitis (36). These data suggest that the healthy mucosal microenvironment down-regulates mCD14 expression but that inflammatory processes lead to its up-regulation (13,14,19,20,36,42,46).…”

Section: Discussionmentioning

confidence: 98%

“…Furthermore, the anti-inflammatory cytokines IL-4, a prevalent cytokine of the mucosal microenvironment, and IL-13 were reported to down-regulate CD14 expression on monocytes (6,30). Interestingly, human lamina propria macrophages almost do not express mCD14 (19,46) unless inflammation is present, such as in inflammatory bowel disease (20,42) or celiac disease (48). In mice, TNF-␣ and IL-1␤ were shown to induce CD14 mRNA in nonintestinal epithelial cells (13,14).…”

Section: Discussionmentioning

confidence: 99%

CD14 Is Expressed and Released as Soluble CD14 by Human Intestinal Epithelial Cells In Vitro: Lipopolysaccharide Activation of Epithelial Cells Revisited

et al. 2001

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Human endothelial as well as epithelial cells were shown to respond to lipopolysaccharides (LPSs). However, the expression and release of CD14 by these so-called CD14-negative cells have not been studied in detail. We investigated three human intestinal epithelial cell lines (ECLs), SW-480, HT-29, and Caco-2, for their expression of CD14 and CD11c/CD18 as well as their responsiveness to endotoxins. Fluorescence-activated cell sorter analysis revealed no expression of CD11c/CD18, but there was low expression of membrane-bound CD14 on HT-29, Caco-2, and SW-480 ECLs. Both Western blotting and reverse transcription-PCR confirmed the CD14 positivity of all three intestinal ECLs. No substantial modulation of CD14 expression was achieved after 6, 8, 18, 24, and 48 h of cultivation with 10-fold serial dilutions of LPS ranging from 0.01 ng/ml to 100 g/ml. Interestingly, soluble CD14 was found in the tissue culture supernatants of all three ECLs. Finally, only HT-29 and SW-480, and not Caco-2, cells responded to LPS exposure (range, 0.01 ng/ml to 100 g/ml) by interleukin 8 release. Thus, we show that HT-29, SW-480, and Caco-2 human intestinal ECLs express membrane-bound CD14. As Caco-2 cells did not respond to LPS, these cell lines might be an interesting model for studying the receptor complex for LPS. The fact that human intestinal epithelial cells are capable not only of expression but also of release of soluble CD14 may have important implications in vivo, e.g., in shaping the interaction between the mucosal immune system and bacteria in the gut and/or in the pathogenesis of endotoxin shock.Endotoxin, the bacterial lipopolysaccharide (LPS), is a characteristic outer membrane entity of gram-negative bacteria and a potent inducer of inflammatory responses. Exposure to even low amounts of LPS leads to a dramatic release of inflammatory mediators that are thought to be responsible for the deleterious effects in septic shock, such as refractory hypotension, disseminated intravascular coagulation, and multiple organ failure, causing the high mortality rate in gram-negative sepsis (18).Several cell surface structures such as CD11c/CD18, the scavenger receptor, and the D-galactose receptor have been found to bind LPS, as have a number of serum components, namely, albumin, transferrin, bactericidal/permeability-increasing protein (BPI), and high-density lipoproteins. Many of these are involved in LPS detoxification (reviewed in reference 45). On the other hand, CD14, a 53-kDa glycosylphosphatidylinositol (GPI)-anchored protein together with LPS-binding protein (LBP) have been shown to play a substantial role in LPS-mediated cell activation (31, 54). CD14 exists as a membrane GPI-anchored glycoprotein and a soluble plasma protein. Both forms of CD14 were shown to be involved in LPS signaling and cell activation, characterized by induction of tumor necrosis factor alpha (TNF-␣), interleukin 1 (IL-1), 45). While membrane CD14 (mCD14) is involved in LPS activation of CD14-positive cells via complexes of LPS and LBP (21,49,54), so...

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“…They represent one of the largest compartments of the mononuclear phagocyte system in the body (1) and constitute 10 -20% of the mononuclear cells in the lamina propria (2)(3)(4). Intestinal macrophages (IMAC) 4 from normal noninflamed mucosa show a specific nonreactive phenotype with down-regulated monocyte/macrophage surface receptors such as CD14, CD16, CD80, or CD86 (5)(6)(7)(8)(9)(10)(11). It is generally assumed that these nonreactive, anergic cells inhibit immunological responses to Ags present in the intestine under normal conditions.…”

mentioning

confidence: 99%

Physiological Role of Macrophage Inflammatory Protein-3α Induction during Maturation of Intestinal Macrophages

Hausmann

Bataille

Spoettl

et al. 2005

The Journal of Immunology

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Intestinal macrophages (IMAC) are a central component in the defense of the intestinal mucosa against luminal microbes. In normal mucosa, monocytes differentiate to immunologically tolerant IMAC with a typical phenotype lacking activation markers such as CD14 and TLRs 2 and 4. CD33+ IMAC were isolated from normal intestinal mucosa by immunomagnetic beads. A subtractive hybridization subtracting mRNA from normal IMAC from those of in vitro differentiated macrophages was performed. IMAC differentiation was studied in multicellular spheroids (MCS). Functional assays on migration of CD45R0+ T cells were performed in MCS coculture models. Of 76 clones, 3 obtained by subtractive mRNA hybridization showed >99% homology to mRNA of MIP-3α, indicating that this chemokine is induced in IMAC compared with in vitro differentiated macrophages. MIP-3α protein expression was confirmed in cryostat sections of normal intestinal mucosa by immunohistochemistry. IMAC in the lamina propria stained positive for MIP-3α. FACS of purified IMAC clearly indicated expression of MIP-3α in these cells. In the MCS-in vitro differentiation model for IMAC, MIP-3α protein expression was absent on day 1 but detectable on day 7 of coculture, demonstrating the induction of MIP-3α during differentiation of IMAC. IMAC attracted CD45R0+ T cells to migrate into an MCS coculture model. In human mucosa, a close contact between IMAC and CD45R0+ T cells could be demonstrated. MIP-3α is induced during the differentiation of monocytes into IMAC. Our data suggest that MIP-3α expression could be involved in the recruitment of CD45R0+ cells into the lamina propria.

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T-cell co-stimulatory molecules are upregulated on intestinal macrophages from inflammatory bowel disease mucosa

Cited by 48 publications

References 0 publications

B7-DC Regulates Asthmatic Response by an IFN-γ-Dependent Mechanism

B7-DC Regulates Asthmatic Response by an IFN-γ-Dependent Mechanism

CD14 Is Expressed and Released as Soluble CD14 by Human Intestinal Epithelial Cells In Vitro: Lipopolysaccharide Activation of Epithelial Cells Revisited

Physiological Role of Macrophage Inflammatory Protein-3α Induction during Maturation of Intestinal Macrophages

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