Counter-Antigen Presentation: Fibroblasts Produce Cytokines by Signalling Through Hla Class Ii Molecules Without Inducing T-Cell Proliferation

Ohyama, Hideki; Nishimura, Fusanori; Meguro, Michio; Takashiba, Shogo; Murayama, Yoji; Matsushita, Sho

doi:10.1006/cyto.2001.0976

Cited by 31 publications

(34 citation statements)

References 29 publications

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“…11 RANTES, MCP-1, IL-8, and IL-6 were detected in both DR-sup and DQ-sup as shown previously, and each cytokine or chemokine concentrations was similar to our previous data 11 (data not shown). There was little difference in the total amounts of these cytokines between DR-sup and DQ-sup in each HGF donor cell line tested in this study.…”

Section: The Expression Of Hla II Molecules On Hgfsupporting

confidence: 90%

“…9, 10 We previously showed that fibroblasts secrete several cytokines, such as regulated upon activation, normal T cells expressed and secreted (RANTES), MCP-1, IL-8, and IL-6, when HLA-II molecules on the fibroblast surface are crosslinked with monoclonal antibodies (mAbs) or when a complex is formed comprising antigenic peptides, TCRs, and HLA-II molecules. 11 As proliferative responses of T-cell clones were not observed in the co-culture system with antigen-presenting fibroblasts in that study, we proposed that HLA-II molecules expressed on the cell surface of fibroblasts act chiefly as receptor molecules to induce the cells to produce soluble factors, including cytokines and chemokines, rather than as antigenpresenting molecules to activate T cells. It is therefore likely that products from fibroblasts activated by HLA-II signaling would also regulate Th-cell activation and differentiation in response to antigenic peptides presented by APCs including DCs.…”

mentioning

confidence: 72%

“…Previously, we reported that fibroblasts produce several cytokines such as RANTES, MCP-1, IL-6, IL-8, and the growth-related gene product following HLA-II stimulation. 11,18 These results suggested that fibroblasts stimulated thus might act in the recruitment of immunological cells and angiogenesis at sites of inflammatory lesions. Accordingly, this study estimated the effects of soluble factors from HLA-II-stimulated fibroblasts on the immunological responses mediated by Th cells.…”

Section: The Effects Of the Culture Supernatants Of Th Cells Activatementioning

confidence: 87%

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Fibroblasts stimulated via HLA-II molecules produce prostaglandin E2 and regulate cytokine production from helper T cells

Kato-Kogoe

Ohyama

Nishimura

et al. 2010

Laboratory Investigation

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Fibroblasts act as important immune regulatory cells via their ability to cross-talk with T cells accumulating in lesions.Our previous study showed that fibroblasts produce several cytokines and chemokines by crosslinking HLA class II (HLA-II) molecules with monoclonal antibodies or by making T-cell receptor-peptide-HLA complexes. It is thus conceivable that the interaction of T cells and fibroblasts via HLA-II affects fibroblast responses to stimuli. This study used human gingival fibroblasts (HGF) to investigate possible effects of these fibroblast-derived soluble factors on the differentiation of naïve T cells and on the subsequent fibroblast responses. After mixed lymphocyte reaction culture between naïve T cells and allogeneic dendritic cells in the presence of culture supernatant from HGF stimulated via HLA-DQ molecules (DQ-sup), but not via DR, T cells exhibited a Th2-shifted phenotype, thereby producing quantitatively more IL-13 and IL-5 compared with interferon-g. Astonishingly, analyses to identify possible factors affecting the Th2 polarization secreted from HLA-IIstimulated HGF, prostaglandin E 2 , was detected only in DQ-sup. The Th2 polarization of naïve T cells was blocked in the presence of supernatants from indomethacin-treated HGF with HLA-DQ stimulation. In addition, we found that the culture supernatants of Th cells activated following mixed lymphocyte reaction culture in the presence of DQ-sup had the potential to induce gene expression of type I and III collagens in HGF. These results suggested that fibroblasts stimulated via HLA-DQ molecules promote Th2 polarization in Th-cell responses and showed the counter activation of collagen synthesis, implicating orchestrated responses among these cells in the fibrosis of chronic inflammatory lesions.

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Section: The Expression Of Hla II Molecules On Hgfsupporting

confidence: 90%

mentioning

confidence: 72%

Section: The Effects Of the Culture Supernatants Of Th Cells Activatementioning

confidence: 87%

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Fibroblasts stimulated via HLA-II molecules produce prostaglandin E2 and regulate cytokine production from helper T cells

Kato-Kogoe

Ohyama

Nishimura

et al. 2010

Laboratory Investigation

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“…The repertoire of costimulatory receptors expressed depends upon the activation state of the T lymphocyte. Myofibroblasts and fibroblasts in different organs variably express costimulatory molecules that influence T cell proliferation (54,57,58,60). Our FACS analysis of freshly isolated CMFs revealed that these cells expressed costimulatory molecules of the B7 family, CD80 and CD86.…”

Section: Discussionmentioning

confidence: 83%

Subepithelial Myofibroblasts are Novel Nonprofessional APCs in the Human Colonic Mucosa

Saada¹,

Pinchuk²,

Barrera³

et al. 2006

The Journal of Immunology

110

139

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The human gastrointestinal mucosa is exposed to a diverse normal microflora and dietary Ags and is a common site of entry for pathogens. The mucosal immune system must respond to these diverse signals with either the initiation of immunity or tolerance. APCs are important accessory cells that modulate T cell responses which initiate and maintain adaptive immunity. The ability of APCs to communicate with CD4+ T cells is largely dependent on the expression of class II MHC molecules by the APCs. Using immunohistochemistry, confocal microscopy, and flow cytometry, we demonstrate that α-smooth muscle actin+, CD90+ subepithelial myofibroblasts (stromal cells) constitutively express class II MHC molecules in normal colonic mucosa and that they are distinct from professional APCs such as macrophages and dendritic cells. Primary isolates of human colonic myofibroblasts (CMFs) cultured in vitro were able to stimulate allogeneic CD4+ T cell proliferation. This process was dependent on class II MHC and CD80/86 costimulatory molecule expression by the myofibroblasts. We also demonstrate that CMFs, engineered to express a specific DR4 allele, can process and present human serum albumin to a human serum albumin-specific and DR4 allele-restricted T cell hybridoma. These studies characterize a novel cell phenotype which, due to its strategic location and class II MHC expression, may be involved in capture of Ags that cross the epithelial barrier and present them to lamina propria CD4+ T cells. Thus, human CMFs may be important in regulating local immunity in the colon.

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“…Fibroblasts are mostly immunologically toleranst [30]. Xenogenic fibroblasts have less tendency to tissue rejection as they expressed HLA without inducing T-cell proliferation [31]. Bone marrow stem cells and mesenchymal stem cells (MSCs) have shown the potential in vivo immune modulation and immune privileged properties [32–35].…”

Section: Discussionmentioning

confidence: 99%

Chitosan Dermal Substitute and Chitosan Skin Substitute Contribute to Accelerated Full-Thickness Wound Healing in Irradiated Rats

Hilmi

Halim

Jaafar

et al. 2013

BioMed Research International

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Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%), longest epithelial tongue (1.62 ± 0.13 mm), and shortest migratory tongue distance (7.11 ± 0.25 mm). The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm) and chitosan skin substitute (0.16 ± 0.05 cm) were significantly decreased (P < 0.05) compared with duoderm (0.45 ± 0.11 cm). Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation.

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Counter-Antigen Presentation: Fibroblasts Produce Cytokines by Signalling Through Hla Class Ii Molecules Without Inducing T-Cell Proliferation

Cited by 31 publications

References 29 publications

Fibroblasts stimulated via HLA-II molecules produce prostaglandin E2 and regulate cytokine production from helper T cells

Fibroblasts stimulated via HLA-II molecules produce prostaglandin E2 and regulate cytokine production from helper T cells

Subepithelial Myofibroblasts are Novel Nonprofessional APCs in the Human Colonic Mucosa

Chitosan Dermal Substitute and Chitosan Skin Substitute Contribute to Accelerated Full-Thickness Wound Healing in Irradiated Rats

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