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

Hausmann, Martin; Bataille, Frauke; Spoettl, Tanja; Schreiter, K.; Falk, Werner; Schöelmerich, Juergen; Herfarth, Hans H; Rogler, Gerhard

doi:10.4049/jimmunol.175.3.1389

Cited by 18 publications

(17 citation statements)

References 64 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased MIP-3α protein secretion was confirmed by ELISA. In vivo, MIP-3α protein expression in human intestinal epithelial cells and IMACs was determined in a nonquantitative manner by immunohistochemistry and flow cytometry [31]. In this work, we could confirmMIP-3α mRNA expression ex vivo in freshly isolated intestinal epithelial cells and IMACs.…”

Section: Discussionsupporting

confidence: 70%

“…Other cell types, such as endothelial cells, fibroblasts, and monocytes are also known to express MIP-3α [28,30]. High MIP-3α mRNA and protein expression are induced during the specific differentiation of IMACs as shown in previous studies from our laboratory [31]. Similarly, MIP-3α mRNA was found to be highly expressed in differentiated macrophages in the lung [28].…”

Section: Introductionmentioning

confidence: 77%

“…These data suggest that CCR6 functions on memory T cells that home to mucosal sites as part of an immune response [26]. Professional antigen-presenting and MIP-3α-secreting IMACs may serve as a contact point for CD45R0 + memory T and B cells and subpopulations of DCs [31]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MIP-3α Expression in Macrophages Is NOD Dependent

Hausmann¹,

Zeitler

Weber

et al. 2012

Digestion

View full text Add to dashboard Cite

Background: The first identified susceptibility gene for Crohn’s disease, NOD2, acts as a sensor for the bacterial-wall peptidoglycan fragment muramyl dipeptide (MDP) and activates the transcription factor nuclear factor-ĸB (NF-ĸB). Upon NF-ĸB activation, intestinal macrophages (IMACs) induce expression of macrophage inflammatory protein (MIP)-3α to attract memory T lymphocytes. We therefore investigated the influence of NOD2 ligation of IMAC differentiation and functional MIP-3α induction. Methods: Human embryonal kidney HEK293 cells were transfected with NOD2 wild-type (NOD2^WT) and the NOD2 SNP13 variant (NOD2^L1007fsinsC) and stimulated with MDP. Recruitment of CD45R0⁺ and Th17 cells was determined by immunohistochemistry. Results: Endogenous NOD2 stimulation was followed by a dose-dependent increase in MIP-3α secretion in MONO-MAC-6 (MM6) cells. MIP-3α mRNA was also significantly (* p < 0.05) induced in HEK293 transfected with NOD2^WT via MDP ligation. In vivo cell-cell contacts between IMACs and CD45R0⁺ memory T cells as well as recruitment of Th17 cells in patients of NOD2 variants were unchanged as compared to wild-type patients. Conclusion: Our data demonstrate a dose-dependent increase in MIP-3α secretion in the human myeloid cell line MM6 upon MDP. However, MIP-3α-driven recruitment of Th17 cells or CD45R0⁺ memory T lymphocytes is not affected in patients carrying heterozygous NOD2 variants.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 77%

See 1 more Smart Citation

MIP-3α Expression in Macrophages Is NOD Dependent

Hausmann¹,

Zeitler

Weber

et al. 2012

Digestion

View full text Add to dashboard Cite

show abstract

“…Under inflammatory conditions, epithelial cells [31], endothelial cells, fibroblasts, and monocytes are thought to be important sources of CCL20 production [16,32]. Similarly, some studies have shown that high expression of CCL20 is induced in differentiated macrophages in intestinal epithelium [33] and lung [32]. In human inflamed pulp sections, CCL20 is mostly expressed by macrophages accumulated in the area adjacent to carious lesions and CCR6 expression is also elevated in inflammatory infiltrating lymphocytes, which suggest that CCL20 may play a major role in the advancement of pulpal inflammation via the recruitment of CCR6-expressing lymphocytes [34].…”

Section: Discussionmentioning

confidence: 99%

Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages

Laumonnier

Syrovets

et al. 2013

ABBS

View full text Add to dashboard Cite

In the present study, monocyte-derived human macrophages were differentiated from buffy coats. Naïve CD4 1 T-cells enriched from peripheral blood mononuclear cells using anti-CD4 magnetic beads and the autoMACS separation system were polarized under T-helper 17 (Th17)-promoting conditions for 6 days to get Th17 cells. The frequency of Th17 cell differentiation and the expression of C-C chemokine receptor type 6 (CCR6) on Th17 cells were investigated by flow cytometry. Plasmin-triggered induction of macrophage inflammatory protein-3alpha/C-C chemokine ligand 20 (CCL20) genes in macrophages was assessed by reverse transcription-polymerase chain reaction, and secreted protein levels were measured by enzymelinked immunosorbent assay. Th17 cell migration induced by CCL20 secreted from plasmin-stimulated macrophages was tested in vitro by chemotaxis using a transwell system. These results demonstrate that plasmin triggers the expression of chemokine CCL20 messenger RNA and the release of CCL20 protein in human monocyte-derived macrophages, which critically depend on the proteolytic activity of plasmin and activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways. Expression of CCR6 was detected on 87.23 + + + + + 8.6% of Th17 cells in vitro. Similar to chemotaxis triggered by recombinant human CCL20, supernatants collected from plasmin-stimulated macrophage-induced chemotactic migration of Th17 cells, which could be inhibited by an anti-CCL20 neutralizing antibody. These results suggest that plasmin generated in inflamed tissues might elicit production of chemokine CCL20 by human macrophages leading to the recruitment of CCR6 positive Th17 cells to the inflammatory sites.

show abstract

“…In IBD this differentiation is altered at sites of inflammation [16,17,18,19,20,21,22,23]. A different phenotype with different functional properties occurs [16,17,18,19,20,21,22,23,24]. …”

Section: Tissue-specific Differentiation Of Innate Immune Cellsmentioning

confidence: 99%

The Innate Immune System: A Trigger for Many Chronic Inflammatory Intestinal Diseases

Kamada

Rogler

2016

Inflamm Intest Dis

Self Cite

View full text Add to dashboard Cite

Background: Mononuclear phagocytes, such as monocytes, macrophages, and dendritic cells, are important cellular components of the innate immune system that contribute to the pathogenesis of many intestinal inflammatory diseases. Summary: While mononuclear phagocytes play a key role in the induction of inflammation in many different tissues through production of pro-inflammatory cytokines and chemokines (such as IL-1, TNF, IL-6, IL-8 and MCP-1), free oxygen radicals (also termed ‘oxidative burst'), proteases (such as cathepsins) and tissue-degrading enzymes (such as metalloproteinases), resident macrophages as well as dendritic cells in the intestine display an anergic and ‘tolerogenic' phenotype mediating tolerance to commensal bacteria. In recent years many single nucleotide polymorphisms (SNPs) in genes mainly expressed in the above-mentioned cell types have been identified to convey an increased risk of autoimmune diseases. SNPs in the NOD2, ATG16L1 and TNFSF15 genes, which are involved in the function of the innate immune cells, are identified as risk factors for Crohn's disease (CD). Of note, these genes are involved in the different functions in the innate immune cells. For example, while NOD2 is required for intracellular recognition of microbial components, ATG16L1 is involved in autophagy responses against intracellular microbes. Likewise, TNFSF15 contributes to the induction of inflammatory responses by innate immune cells. Furthermore, the frequency of mutations in these genes differs by ethnicity. Genetic variations in the NOD2 and ATG16L1 genes are associated with CD in Caucasians but much less in Eastern Asian populations, whereas SNPs in TNFSF15 are dominated in Asian populations. Thus, different genetic risks may eventually lead to similar impairments in innate immune cells, thereby developing the same disease in Western and Asian patients with CD. Key Messages: Despite differences in risk genes, similar mechanisms associated with the innate immune system may trigger autoimmune and chronic inflammatory intestinal diseases in East and West.

show abstract

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

Cited by 18 publications

References 64 publications

MIP-3α Expression in Macrophages Is NOD Dependent

MIP-3α Expression in Macrophages Is NOD Dependent

Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages

The Innate Immune System: A Trigger for Many Chronic Inflammatory Intestinal Diseases

Contact Info

Product

Resources

About