Overexpression of the suppressor of cytokine signalling 3 (SOCS3) in severe atopic dermatitis.

Horiuchi, Yasuhiro; Sj, Bae; Katayama, Ichiro

doi:10.1111/j.1365-2230.2005.01979.x

Cited by 22 publications

(18 citation statements)

References 16 publications

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“…In line with this, the increased SOCS3 expression in T cells correlated with the severity of asthma and atopic dermatitis or with the Th1-mediated condition psoriasis (91, 120, 121). Furthermore, defined haplotypes of SOCS3 have been linked with atopic dermatitis in childhood cohorts (121).…”

Section: Socs3 and T Cellssupporting

confidence: 69%

SOCS3, a Major Regulator of Infection and Inflammation

2014

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In this review, we describe the role of suppressor of cytokine signaling-3 (SOCS3) in modulating the outcome of infections and autoimmune diseases as well as the underlying mechanisms. SOCS3 regulates cytokine or hormone signaling usually preventing, but in some cases aggravating, a variety of diseases. A main role of SOCS3 results from its binding to both the JAK kinase and the cytokine receptor, which results in the inhibition of STAT3 activation. Available data also indicate that SOCS3 can regulate signaling via other STATs than STAT3 and also controls cellular pathways unrelated to STAT activation. SOCS3 might either act directly by hampering JAK activation or by mediating the ubiquitination and subsequent proteasome degradation of the cytokine/growth factor/hormone receptor. Inflammation and infection stimulate SOCS3 expression in different myeloid and lymphoid cell populations as well as in diverse non-hematopoietic cells. The accumulated data suggest a relevant program coordinated by SOCS3 in different cell populations, devoted to the control of immune homeostasis in physiological and pathological conditions such as infection and autoimmunity.

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Section: Socs3 and T Cellssupporting

confidence: 69%

SOCS3, a Major Regulator of Infection and Inflammation

2014

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“…The ratio of SOCS3-positive area to the entire junctional or lesional zones was also significantly higher in junctional zones (Figure 5C; right panel). Weak SOCS3 expression in normal human skin was shown to be almost the same as that in psoriasis lesional skin (Horiuchi et al, 2006). Similar results were noted in two additional psoriatic patients (data not shown).…”

Section: Resultsmentioning

confidence: 99%

CXCR4 Negatively Regulates Keratinocyte Proliferation in IL-23-Mediated Psoriasiform Dermatitis

Takekoshi

Mitsui

et al. 2013

Journal of Investigative Dermatology

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CXCR4 is expressed by basal keratinocytes (KCs), but little is known about its function in inflamed skin. We crossed K14-Cre and CXCR4flox/flox (f/f) transgenic mice, resulting in mice with specific loss of the CXCR4 gene in K14-expressing cells (K14-CXCR4KO), including basal KCs. K14-CXCR4KO pups had no obvious skin defects. We compared K14-CXCR4KO and CXCR4f/f control mice in an IL-23-mediated psoriasisform dermatitis model and measured skin edema, histologic, and immunohistological changes. IL-23-treated K14-CXCR4KO mice showed a 1.3-fold increase in mean ear swelling, 2-fold increase in epidermal thickness, and greater parakeratosis. IL-23-treated WT mice showed weak CXCR4 expression in areas of severe epidermal hyperplasia, but strong CXCR4 expression in non-hyperplastic regions, suggesting CXCR4 may regulate keratinocyte proliferation. To test this hypothesis, we overexpressed CXCR4 in HaCaT keratinocyte cells and treated them with IL-22 and/or CXCL12. CXCL12 blocked IL-22-mediated HaCaT cell proliferation in vitro and synergized with IL-22 in upregulating SOCS3, a key regulator of STAT3. SOCS3 was required for CXCR4-mediated growth inhibition. In human psoriatic skin, both CXCR4 and SOCS3 were upregulated in the junctional region at the border of psoriatic plaques. Thus, CXCR4 plays an unexpected role in inhibiting KC proliferation and mitigating the effects of proliferative Th17 cytokines.

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“…A tendency for increased cutaneous HO‐1 expression was observed in patients with atopic eczema ( P = 0.15). Interestingly, HO‐1 expression exhibited a comparable pattern as expression of the SOCS1 and SOCS3 molecules which have been implicated to be involved in the counter‐regulation of skin inflammation and in type 2 immunodeviation (23–25). When analysing samples from all groups ( n = 18), a significant correlation between HO‐1 and SOCS1 ( r = 0.693; P = 0.001) as well as SOCS3 expression ( r = 0.503; P = 0.03) was observed.…”

Section: Resultsmentioning

confidence: 99%

Heme oxygenase‐1 inhibits T cell‐dependent skin inflammation and differentiation and function of antigen‐presenting cells

Listopad

Asadullah

Sievers

et al. 2007

Experimental Dermatology

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Heme oxygenase-1 (HO-1) is increased in psoriatic skin. We asked for the impact of physiological and pharmacological HO-1 induction on skin immunity and the mechanisms involved in HO-1-induced immunomodulation. We found cutaneous HO-1 expression upregulated comparable with suppressors of cytokine signalling (SOCS)1 and SOCS3 in psoriasis and atopic eczema and temporarily increased in murine ovalbumin-induced late phase reaction (LPR) and 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS). Cutaneous inflammation was enhanced by HO-1 inhibition and was abrogated by treatment with the HO-1 inducer cobaltic protoporphyrin (CoPP) both when applied around sensitization or before challenge. HO-1 inhibition specifically prevented the anti-inflammatory CoPP effect. CoPP inhibited T cell proliferation in splenocytes of treated mice and in human mixed leukocyte reaction and lymphocyte transformation test. CoPP induced HO-1 in antigen-presenting cells and depressed monocytic accessory molecule expression and the differentiation and maturation of monocyte-derived dendritic cells (MDDC). It decreased tumor necrosis factor (TNF)-alpha and interleukin (IL)-12 production while increasing IL-10 secretion. The antigen-presenting capacity was diminished in CoPP-treated and HO-1-transduced MDDC. We demonstrate for the first time the physiological role of HO-1 in the limitation of skin inflammation and implement pharmacological HO-1 induction as a therapeutic approach for T cell-dependent inflammatory dermatoses. Suppression of antigen-presenting cells may represent a main anti-inflammatory mechanism of HO-1.

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Overexpression of the suppressor of cytokine signalling 3 (SOCS3) in severe atopic dermatitis.

Cited by 22 publications

References 16 publications

SOCS3, a Major Regulator of Infection and Inflammation

SOCS3, a Major Regulator of Infection and Inflammation

CXCR4 Negatively Regulates Keratinocyte Proliferation in IL-23-Mediated Psoriasiform Dermatitis

Heme oxygenase‐1 inhibits T cell‐dependent skin inflammation and differentiation and function of antigen‐presenting cells

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