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Journal of Investigative Dermatology 01/2013; · 6.31 Impact Factor
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Makoto Sugaya,
Tomomitsu Miyagaki,
Hanako Ohmatsu,
Hiraku Suga, Hiromichi Kai,
Masahiro Kamata,
Hideki Fujita,
Yoshihide Asano,
Yayoi Tada,
Takafumi Kadono,
Hitoshi Okochi,
Shinichi Sato
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ABSTRACT: Classically activated macrophages produce IL-12, IL-23, and TNF-α, whereas alternatively activated macrophages (M2 cells) produce IL-10 and express several receptors such as mannose receptor and CD163. Tumor-associated macrophages exhibit M2 phenotype, whose presence has been associated with poor prognosis in various tumors.
To investigate distribution of CD163(+) cells in lesional skin and serum levels of soluble CD163 (sCD163) in patients with cutaneous T cell lymphoma (CTCL), atopic dermatitis (AD), or psoriasis.
The numbers of CD163(+) and CD68(+) cells in lesional skin of CTCL, AD, or psoriasis, and in normal skin were examined by immunohistochemistry. Serum soluble CD163 (sCD163) levels were quantified by enzyme-linked immunosorbent assay.
The numbers of CD163(+) cells in lesional skin of CTCL, AD, or psoriasis were significantly larger than in normal skin. In CTCL, the numbers of CD163(+) or CD68(+) cells increased as more tumor cells infiltrated and they decreased after treatment with topical steroid and ultraviolet light. Moreover, CTCL patients with an increased number of CD163(+) cells showed worse prognosis. Serum sCD163 levels in patients with CTCL, AD, or psoriasis were significantly higher than those in normal controls. In CTCL patients, serum sCD163 levels significantly correlated with serum soluble interleukin-2 receptor and CCL17 levels. In AD patients, serum sCD163 levels correlated with serum IgE levels.
The numbers of CD163(+) cells in lesional skin and serum sCD163 levels were associated with disease progression of CTCL. Further study focusing on CD163(+) cells in CTCL lesional skin would be an interesting research field.
Journal of dermatological science 07/2012; 68(1):45-51. · 3.71 Impact Factor
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Hanako Ohmatsu,
Makoto Sugaya,
Hiraku Suga,
Sohshi Morimura,
Tomomitsu Miyagaki, Hiromichi Kai,
Shinji Kagami,
Hideki Fujita,
Yoshihide Asano,
Yayoi Tada,
Takafumi Kadono,
Shinichi Sato
Acta Dermato-Venereologica 03/2012; 92(3):282-3.
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Journal of Investigative Dermatology 09/2011; 132(1):249-51. · 6.31 Impact Factor
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ABSTRACT: C-C chemokine receptor (CCR)10 is a specific receptor for chemokine ligand (CCL)27, a selective chemoattractant for skin-associated memory T cells to cutaneous sites. In melanoma, CCR10 increases the ability of neoplastic cells to grow, invade tissues, disseminate to lymph nodes, and escape the host immune responses. In this study, we investigated the expression of CCR10 and its ligand CCL27 in squamous cell carcinoma (SCC). CCR10 and CCL27 were expressed in SCC, actinic keratosis (AK), Bowen's disease, and seborrheic keratosis (predominantly prickle cell type), but not in seborrheic keratosis (predominantly basal cell type) and basal cell carcinoma. Furthermore, CCR10 and CCL27 were overexpressed in SCC relative to Bowen's disease, an early stage of SCC. Consistently, a human SCC cell line, A253 cells, and HaCaT cells exhibited CCL27 production that was strongly induced by tumor necrosis factor-α and interleukin-1β. Finally, A253 cells expressed stronger intracellular CCR10 compared to HaCaT cells by flow cytometry. These results suggest that CCR10 and CCL27 overexpression in SCC is related to the progression of SCC and is useful for the diagnosis of SCC.
Pathology - Research and Practice 01/2011; 207(1):43-8. · 1.21 Impact Factor
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Hanako Ohmatsu,
Takafumi Kadono,
Makoto Sugaya,
Manabu Tomita, Hiromichi Kai,
Tomomitsu Miyagaki,
Hidehisa Saeki,
Kunihiko Tamaki,
Douglas A Steeber,
Thomas F Tedder,
Shinichi Sato
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ABSTRACT: β7 Integrin, a cell adhesion molecule, is present in the form of α4β7 integrin or αEβ7 integrin. α4β7 Integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, mucosal addressin cell adhesion molecule-1, which is preferentially expressed in gut-associated lymphoid tissues. Although the importance of α4β7 integrin in intestinal inflammation has been established, its role in cutaneous inflammation remains to be elucidated.
We sought to investigate the role of β7 integrin in cutaneous inflammation.
We used a murine contact hypersensitivity model and examined the role of β7 integrin by using β7 integrin-deficient and αE integrin-deficient mice.
β7 Integrin-deficient mice, not αE integrin-deficient mice, are defective in contact hypersensitivity responses. β7 Integrin deficiency does not affect irritant contact dermatitis. The distribution, migration, and function of antigen presenting cells from β7 integrin-deficient mice are comparable to those from wild-type mice. Moreover, sensitized β7 integrin-deficient T cells are able to respond to antigen stimuli in vitro and elicit contact hypersensitivity responses when directly injected into the skin. However, they are defective in reaching the skin under inflammatory conditions, resulting in reduced contact hypersensitivity responses when intravenously injected. Furthermore, intraperitoneal injection of anti-α4β7 integrin neutralizing antibody elicit impaired contact hypersensitivity responses.
α4β7 Integrin contributes to contact hypersensitivity responses by regulating T-cell migration to inflammatory skin.
The Journal of allergy and clinical immunology 11/2010; 126(6):1267-76. · 9.17 Impact Factor
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Sayaka Shibata,
Yayoi Tada,
Naoko Kanda,
Kiyoko Nashiro,
Masahiro Kamata,
Masaru Karakawa,
Tomomitsu Miyagaki, Hiromichi Kai,
Hidehisa Saeki,
Yuji Shirakata,
Shinichi Watanabe,
Kunihiko Tamaki,
Shinichi Sato
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ABSTRACT: The immunological significance of IL-27 has been reported and discussed in various Th1/Th17-mediated inflammatory diseases. However, its importance in psoriasis is unknown. We investigated pathophysiological roles of IL-27 in psoriasis in this study. Serum IL-27 levels in psoriatic patients were significantly higher than those in healthy controls, and correlated with disease severity and serum IFN-gamma levels. An immunohistochemical analysis revealed the infiltration of IL-27-secreting cells in the papillary dermis of psoriatic skin lesions but not in skin lesions with atopic dermatitis or normal skin. Furthermore, IL-27 alone greatly induced in vitro CXCL9, CXCL10, and CXCL11 production and tyrosine phosphorylation of signal transducer and activator of transcription 1 in normal human keratinocytes, while it suppressed the tumor necrosis factor-alpha-induced production of IL-1alpha and CCL20. These results indicate that IL-27 may promote the onset of psoriasis, while it may simultaneously attenuate the expanded inflammation in this disease. Our results implicate potential therapeutic effects of IL-27 for psoriasis.
Journal of Investigative Dermatology 11/2009; 130(4):1034-9. · 6.31 Impact Factor
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The Journal of Dermatology 12/2007; 34(11):795-7. · 1.49 Impact Factor
