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355 NKG2D is highly expressed on IFNγ producing skin CD8+ effector memory T cells in vitiligo
Inflammation, Immunity and Infection | ABSTRACTS 352
Neuromedin U directly activates human and mouse skin mast cells Y Matsuo1, Y Yanase1, S Tanaka2, K Furuta2 and M Hide1 1 Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, Hiroshima, Japan and 2 Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentisty, and Pharmaceutical Sciences, Okayama University, Japan, Okayama, Japan Mast cells play critical roles for innate and acquired immune responses by release of chemical mediators, such as histamine and lipid mediators, in response to various stimuli through IgE receptor-dependent or -independent pathways. Recent reports suggest that a neuropeptide, neuromedin-U (NMU), induces an early inflammatory response by directly activating mast cells in mouse and that NMU-deficient mice are protected from developing autoantibody-induced inflammatory arthritis. However, detailed mechanism of NMUinduced mast cells activation has not been clarified. In this study, we investigated the effects of NMU on the activation of mouse bone marrow-derived mast cells (BMMCs), connectivetissue type mouse mast cells differentiated from BMMCs (CTMCs), and human skin derived mast cells (HSMCs) in vitro. NMU induced the degranulation of CTMCs and HSMCs, but not BMMCs, in a concentration-dependent manner. Moreover, the degranulation of CTMCs and HSMCs was clearly inhibited by the treatment with pertussis toxin, suggesting that NMU activates mast cells via Gi /o protein-coupled receptor. Although no or only slight NMU receptors (NMUR1) were expressed in CTMCs and HSMCs, Mas-related gene (Mrg) X2 (MrgX2) and Mrgb2, mouse analog of MrgX2 were highly expressed in HSMCs and in CTMCs, respectively, but not in BMMCs at mRNA level. Moreover, we confirmed that NMU directly bound and activated MrgX2 by means of TGFa shedding assay. We here demonstrated that NMU induced the activation of human and mouse skin mast cells via Mrg receptors. In skin, large amount of NMU are expressed in keratinocytes and peripheral nerve, suggesting that NMU, presumably released from keratinocytes and nerve terminals, may activate skin mast cells via MrgX2. Development of specific antagonist of MrgX2 may be a potent therapeutic tool to regulate the activation of mast cells.
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AntieSaccharomyces cerevisiae antibodies (ASCA) are biomarkers of moderate-to-severe hidradenitis suppurativa (HS), but not of severe plaque psoriasis: Results from a prospective, multicenter study J Gottlieb1, G Hickman1, N Guigue2, E Pape3, S Lebbah4, E Delaporte3, B Sendid5, F Aubin6, F Tubach4 and H Bachelez7,1 1 Dermatology, APHP Saint Louis, Paris, France, 2 APHP Saint Louis, Paris, France, 3 Dermatology, CHRU, Lille, France, 4 Statistics, APHP, Paris, France, 5 Inserm U995, Lille, France, 6 Dermatology, CHRU, Besanc¸on, France and 7 INSERM UMR1163, Institut Imagine, Paris, France ASCA, a serological biomarker for Crohn’s disease (CD) and spondylarthritis, is thought to be linked to dysbiosis, but its prevalence has never been assessed in HS. In a multicenter study between 2012 and 2017, we prospectively and comparatively assessed by ELISA the serological concentration and isotype (IgG and/or IgA) of ASCA in consecutive patients with HS (n¼148), with plaque psoriasis candidate for systemic therapy (n¼159) and in healthy donors (HD, n¼162). Positivity was defined by a concentration of at least 25 UA/ml for IgG or IgA. Data analysis was performed using R software (Chi square and Fischer’s exact test). ASCA were detected in 24.3% of HS cases versus 4.4% and 4.3% for psoriasis and HD respectively (p<0.001). In HS group, prevalence of ASCA was significantly higher in patients Hurley stage III (41.8%) over those Hurley stages I or II (13.8%, p¼0.001), and in those with a C-reactive protein (CRP) serum level >15 mg/l (57.1% vs 15.8% in those with CRP <15 mg/l, p<0.001), and in nonsmokers over active smokers (35.6% vs 16.1%, p¼0.007), while no correlation was found with body mass index. We obtained the same trend in sensitivity analysis in patients with only IgA or IgG isotypes (12.8% IgG in HS vs respectively 2.5% and 1.9% for psoriasis and HD, p<0.001). IgG ASCA were detected in 36.8% of HS patients with arthritis (vs 9.3% without, p¼0.004), while difference was not significant for IgA. These results identify for the first time ASCA IgG and/or IgA as biomarkers of HS, mainly in its moderate-to-severe forms, and provide support for the existence of dysbiosis in HS, all features which seem to differ from psoriasis, while being reminiscent of CD and spondylarthritis immunopathological models.
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Identification of the epidermal miRNome in psoriasis skin A Srivastava1, L Pasquali1, F Meisgen 1 , M Mona Sta˚hle1,2 , N Xu Lande´n1 , A Pivarcsi1 and E Sonkoly1,2 1 Dept of Medicine, Dermatology and Venereology Unit, Karolinska Institutet, Stockholm, Sweden and 2 Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden Psoriasis is a common chronic inflammatory skin disease, in which chronic skin inflammation is thought to be a result of interactions between keratinocytes and the immune system. MicroRNAs (miRNAs) are short noncoding RNAs that regulate the expression of the majority of protein-coding genes and are thus potent regulators of cellular functions. We have previously identified miRNAs deregulated in psoriasis skin, which regulate keratinocyte and/or immune cell functions. Here, we analyzed the cell-specific miRNome in epidermal cells in psoriasis, by next-generation sequencing (RNAseq) of small RNAs in CD45- (non-immune) epidermal cells sorted from the lesional and non-lesional skin of psoriasis patients, and from healthy skin of control subjects. This approach enabled us to study the keratinocyte-specific miRNome in psoriasis, which in previous studies utilizing full-depth biopsies, may have been masked by expression in other cell types. Our results revealed differential expression of 104 miRNAs in the epidermal cells in psoriasis lesions, including known and novel miRNAs that have not been previously associated with psoriasis. MiR-149 was identified as one of the significantly downregulated miRNAs in psoriatic epidermal cells. qPCR analysis confirmed its downregulation in psoriatic lesional epidermal cells as compared to those from non-lesional or normal skin. Notably, miR-149 was previously shown to have anti-inflammatory functions in other cell types. Taken together, our results identified the miRNA landscape in epidermal non-immune cells, and identified known and novel miRNAs previously not associated with psoriasis. These results can provide a basis for further functional studies of miRNAs in keratinocytes, which can identify miRNAs that can be targeted for topical therapy.
NKG2D is highly expressed on IFNg producing skin CD8+ effector memory T cells in vitiligo C Jacquemin1, C Martins1, A Taieb1,2, J Seneschal1,2 and K Boniface1 1 Immuno-dermatology, Universite´ de Bordeaux, Bordeaux, France and 2 Department of Dermatology and Pediatric Dermatology, Hoˆpital Saint Andre´, Bordeaux, France Vitiligo is an autoimmune disease that results from the loss of epidermal melanocytes. During progression of the disease, vitiligo skin is infiltrated by IFNg-producing CXCR3+ CD8+ Effector Memory T (TEM) cells that contribute to disease pathogenesis. Natural Killer (NK) Group 2D (NKG2D) is an activating receptor mainly found on immune cells, including NK and CD8+ T cells. NKG2D+ CD8+ T cells are important during immune surveillance and skin immune diseases, such as alopecia areata. To date, the involvement of NKG2D in vitiligo pathogenesis remains unknown. Here, we show that expression of NKG2D, that also defines a Tc1 profile, is up-regulated on skin CD8+ TEM in progressive vitiligo compared to stable vitiligo or psoriasis. A thorough analysis of extracted skin T cells showed that NKG2D+ CD8+ TEM cells express markers of residency such as CD69, CD49a and/or CD103 and produce elevated levels of both IFNg and TNF-a. Moreover, we found a positive correlation between expression of CXCR3 and NKG2D on CD8+ TEM cells. In additional in vitro experiments, isolated vitiligo skin NKG2D+ CD8+ TEM cells displayed higher capacity of activation and proliferation compared to NKGD2- CD8+ TEM cells. All together, these data highlight NKG2D as a potential marker of pathogenic CD8+ TEM cells important for vitiligo progression. Therefore, developing strategies that target NKG2D expressing CD8 TEM cells could be interesting for vitiligo, a disease with high unmet needs.
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An Anti-inflammatory Role for ALK3 in Langerhans Cells M Hochgerner1,2, I Borek2, T Bauer1, M Sibilia1 and H Strobl2 1 Institute of Cancer research, Medical University of Vienna, Vienna, Austria and 2 Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, Austria Langerhans Cells (LCs) represent the epidermal subset of Dendritic Cells (DCs). In their immature state, they are thought to act tolerogenic and play an important role in maintaining skin homeostasis. Formation and maintenance of the LC network are critically dependent on TGF-b1. However, recent studies by our group challenged that view by showing that during in-vitro LC generation TGF-b1 can be replaced by BMP-7. We are therefore hypothesizing that Alk3, a type-1 BMP receptor of the TGF-b-superfamily, is responsible for early differentiation and proliferation. Alk3 can be activated by both TGF-b1 and BMP7. Conversely, Alk5, which is only activated by TGF-b1, might only be necessary for terminal differentiation and network maintenance. In order to test this hypothesis in vivo, we generated several conditional knock-out mice. Alk3Dvav mice, which lack Alk3 in LC precursors, show significantly reduced numbers of LCs and bone-marrow-derived DCs show reduced total cell numbers, supporting a role of Alk3 as mediator of LC differentiation and proliferation. Conversely Alk3DCD11c mice, which lack Alk3 on fully developed DCs, display a normal LC network, indicating that Alk3 is dispensable for network maintenance. However, Alk3DCD11c mice experience a stronger and longer lasting skin inflammation in two different experimental models. LCs from these mice migrate faster with exfiltrating LCs showing stronger expression of MHCII and CD86. Furthermore, we recently observed strong upregulation of BMP-7 and Alk3 signaling in inflamed human psoriatic epidermis. Therefore, we conclude that Alk3 plays an important role in dampening skin inflammation via an LCdependent mechanism. Deeper insight into TGF-b-superfamily signaling in DCs may lead to a better understanding of the mechanisms regulating skin inflammation and might open up new treatment options for diseases like psoriasis.
The role of the galanin system in psoriasis-like skin inflammation F Locker1, S Vidali1, B Holub1,2, J Stockinger1, A Koller1, S Brunner1, D Schwarzenbacher1, R Lang2 and B Kofler1 1 Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria and 2 Department of Dermatology, Paracelsus Medical University, Salzburg, Austria Galanin (GAL) has been shown to be a vasoactive (neuro)-peptide which plays a role in a range of inflammatory diseases. The effects of GAL are mediated via three G protein-coupled receptors (GAL1-3). The aim of the present study was to elucidate which galanin receptor is expressed by endothelial cells and which function this receptor plays in the progression of psoriasis in vitro and in vivo. Healthy and psoriatric human skin was analyzed for expression of GAL1-3 by immunohistochemistry. Psoriasis-like skin inflammation was induced via daily topical application of 5% imiquimod (IMQ) (Aldara) on the shaved and depilated back skin of 8-10 week old male and female GAL2-knockout (KO) and GAL3-KO mice for 6 consecutive days. In healthy human skin GAL3 staining was observed around large, mature vessels. In psoriatric skin GAL3 staining was also observed in large, mature vessels. In addition, in newly formed micro-vessels GAL3 staining co-localized with nestin, a marker of neovascularization. Psoriasis development in skin of GAL3-KO animals resulted in a significant lower psoriasis disease severity score, mRNA levels of IL-17A, IL-22, IL-23 and TNF-a and reduced density of CD31 positive vessels compared to wild types on day 4. Neutrophil derived myeloperoxidase activity was significantly lowered in GAL3-KO mice compared to WT mice which was in line with reduced neutrophil infiltration in psoriatric skin of GAL3-KO mice. The total number of macrophages and mast cells in the skin was not affected by lack of GAL3. GAL2-KO mice did not differ significantly from WT mice at both the macroscopic and molecular levels in their inflammatory response to IMQ treatment. Our data indicate that GAL3, but not GAL2, plays an important role in neovascularization and psoriasis-like skin inflammation.
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Neuromedin U directly activates human and mouse skin mast cells Y Matsuo1, Y Yanase1, S Tanaka2, K Furuta2 and M Hide1 1 Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, Hiroshima, Japan and 2 Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentisty, and Pharmaceutical Sciences, Okayama University, Japan, Okayama, Japan Mast cells play critical roles for innate and acquired immune responses by release of chemical mediators, such as histamine and lipid mediators, in response to various stimuli through IgE receptor-dependent or -independent pathways. Recent reports suggest that a neuropeptide, neuromedin-U (NMU), induces an early inflammatory response by directly activating mast cells in mouse and that NMU-deficient mice are protected from developing autoantibody-induced inflammatory arthritis. However, detailed mechanism of NMUinduced mast cells activation has not been clarified. In this study, we investigated the effects of NMU on the activation of mouse bone marrow-derived mast cells (BMMCs), connectivetissue type mouse mast cells differentiated from BMMCs (CTMCs), and human skin derived mast cells (HSMCs) in vitro. NMU induced the degranulation of CTMCs and HSMCs, but not BMMCs, in a concentration-dependent manner. Moreover, the degranulation of CTMCs and HSMCs was clearly inhibited by the treatment with pertussis toxin, suggesting that NMU activates mast cells via Gi /o protein-coupled receptor. Although no or only slight NMU receptors (NMUR1) were expressed in CTMCs and HSMCs, Mas-related gene (Mrg) X2 (MrgX2) and Mrgb2, mouse analog of MrgX2 were highly expressed in HSMCs and in CTMCs, respectively, but not in BMMCs at mRNA level. Moreover, we confirmed that NMU directly bound and activated MrgX2 by means of TGFa shedding assay. We here demonstrated that NMU induced the activation of human and mouse skin mast cells via Mrg receptors. In skin, large amount of NMU are expressed in keratinocytes and peripheral nerve, suggesting that NMU, presumably released from keratinocytes and nerve terminals, may activate skin mast cells via MrgX2. Development of specific antagonist of MrgX2 may be a potent therapeutic tool to regulate the activation of mast cells.
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AntieSaccharomyces cerevisiae antibodies (ASCA) are biomarkers of moderate-to-severe hidradenitis suppurativa (HS), but not of severe plaque psoriasis: Results from a prospective, multicenter study J Gottlieb1, G Hickman1, N Guigue2, E Pape3, S Lebbah4, E Delaporte3, B Sendid5, F Aubin6, F Tubach4 and H Bachelez7,1 1 Dermatology, APHP Saint Louis, Paris, France, 2 APHP Saint Louis, Paris, France, 3 Dermatology, CHRU, Lille, France, 4 Statistics, APHP, Paris, France, 5 Inserm U995, Lille, France, 6 Dermatology, CHRU, Besanc¸on, France and 7 INSERM UMR1163, Institut Imagine, Paris, France ASCA, a serological biomarker for Crohn’s disease (CD) and spondylarthritis, is thought to be linked to dysbiosis, but its prevalence has never been assessed in HS. In a multicenter study between 2012 and 2017, we prospectively and comparatively assessed by ELISA the serological concentration and isotype (IgG and/or IgA) of ASCA in consecutive patients with HS (n¼148), with plaque psoriasis candidate for systemic therapy (n¼159) and in healthy donors (HD, n¼162). Positivity was defined by a concentration of at least 25 UA/ml for IgG or IgA. Data analysis was performed using R software (Chi square and Fischer’s exact test). ASCA were detected in 24.3% of HS cases versus 4.4% and 4.3% for psoriasis and HD respectively (p<0.001). In HS group, prevalence of ASCA was significantly higher in patients Hurley stage III (41.8%) over those Hurley stages I or II (13.8%, p¼0.001), and in those with a C-reactive protein (CRP) serum level >15 mg/l (57.1% vs 15.8% in those with CRP <15 mg/l, p<0.001), and in nonsmokers over active smokers (35.6% vs 16.1%, p¼0.007), while no correlation was found with body mass index. We obtained the same trend in sensitivity analysis in patients with only IgA or IgG isotypes (12.8% IgG in HS vs respectively 2.5% and 1.9% for psoriasis and HD, p<0.001). IgG ASCA were detected in 36.8% of HS patients with arthritis (vs 9.3% without, p¼0.004), while difference was not significant for IgA. These results identify for the first time ASCA IgG and/or IgA as biomarkers of HS, mainly in its moderate-to-severe forms, and provide support for the existence of dysbiosis in HS, all features which seem to differ from psoriasis, while being reminiscent of CD and spondylarthritis immunopathological models.
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Identification of the epidermal miRNome in psoriasis skin A Srivastava1, L Pasquali1, F Meisgen 1 , M Mona Sta˚hle1,2 , N Xu Lande´n1 , A Pivarcsi1 and E Sonkoly1,2 1 Dept of Medicine, Dermatology and Venereology Unit, Karolinska Institutet, Stockholm, Sweden and 2 Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden Psoriasis is a common chronic inflammatory skin disease, in which chronic skin inflammation is thought to be a result of interactions between keratinocytes and the immune system. MicroRNAs (miRNAs) are short noncoding RNAs that regulate the expression of the majority of protein-coding genes and are thus potent regulators of cellular functions. We have previously identified miRNAs deregulated in psoriasis skin, which regulate keratinocyte and/or immune cell functions. Here, we analyzed the cell-specific miRNome in epidermal cells in psoriasis, by next-generation sequencing (RNAseq) of small RNAs in CD45- (non-immune) epidermal cells sorted from the lesional and non-lesional skin of psoriasis patients, and from healthy skin of control subjects. This approach enabled us to study the keratinocyte-specific miRNome in psoriasis, which in previous studies utilizing full-depth biopsies, may have been masked by expression in other cell types. Our results revealed differential expression of 104 miRNAs in the epidermal cells in psoriasis lesions, including known and novel miRNAs that have not been previously associated with psoriasis. MiR-149 was identified as one of the significantly downregulated miRNAs in psoriatic epidermal cells. qPCR analysis confirmed its downregulation in psoriatic lesional epidermal cells as compared to those from non-lesional or normal skin. Notably, miR-149 was previously shown to have anti-inflammatory functions in other cell types. Taken together, our results identified the miRNA landscape in epidermal non-immune cells, and identified known and novel miRNAs previously not associated with psoriasis. These results can provide a basis for further functional studies of miRNAs in keratinocytes, which can identify miRNAs that can be targeted for topical therapy.
NKG2D is highly expressed on IFNg producing skin CD8+ effector memory T cells in vitiligo C Jacquemin1, C Martins1, A Taieb1,2, J Seneschal1,2 and K Boniface1 1 Immuno-dermatology, Universite´ de Bordeaux, Bordeaux, France and 2 Department of Dermatology and Pediatric Dermatology, Hoˆpital Saint Andre´, Bordeaux, France Vitiligo is an autoimmune disease that results from the loss of epidermal melanocytes. During progression of the disease, vitiligo skin is infiltrated by IFNg-producing CXCR3+ CD8+ Effector Memory T (TEM) cells that contribute to disease pathogenesis. Natural Killer (NK) Group 2D (NKG2D) is an activating receptor mainly found on immune cells, including NK and CD8+ T cells. NKG2D+ CD8+ T cells are important during immune surveillance and skin immune diseases, such as alopecia areata. To date, the involvement of NKG2D in vitiligo pathogenesis remains unknown. Here, we show that expression of NKG2D, that also defines a Tc1 profile, is up-regulated on skin CD8+ TEM in progressive vitiligo compared to stable vitiligo or psoriasis. A thorough analysis of extracted skin T cells showed that NKG2D+ CD8+ TEM cells express markers of residency such as CD69, CD49a and/or CD103 and produce elevated levels of both IFNg and TNF-a. Moreover, we found a positive correlation between expression of CXCR3 and NKG2D on CD8+ TEM cells. In additional in vitro experiments, isolated vitiligo skin NKG2D+ CD8+ TEM cells displayed higher capacity of activation and proliferation compared to NKGD2- CD8+ TEM cells. All together, these data highlight NKG2D as a potential marker of pathogenic CD8+ TEM cells important for vitiligo progression. Therefore, developing strategies that target NKG2D expressing CD8 TEM cells could be interesting for vitiligo, a disease with high unmet needs.
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An Anti-inflammatory Role for ALK3 in Langerhans Cells M Hochgerner1,2, I Borek2, T Bauer1, M Sibilia1 and H Strobl2 1 Institute of Cancer research, Medical University of Vienna, Vienna, Austria and 2 Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, Austria Langerhans Cells (LCs) represent the epidermal subset of Dendritic Cells (DCs). In their immature state, they are thought to act tolerogenic and play an important role in maintaining skin homeostasis. Formation and maintenance of the LC network are critically dependent on TGF-b1. However, recent studies by our group challenged that view by showing that during in-vitro LC generation TGF-b1 can be replaced by BMP-7. We are therefore hypothesizing that Alk3, a type-1 BMP receptor of the TGF-b-superfamily, is responsible for early differentiation and proliferation. Alk3 can be activated by both TGF-b1 and BMP7. Conversely, Alk5, which is only activated by TGF-b1, might only be necessary for terminal differentiation and network maintenance. In order to test this hypothesis in vivo, we generated several conditional knock-out mice. Alk3Dvav mice, which lack Alk3 in LC precursors, show significantly reduced numbers of LCs and bone-marrow-derived DCs show reduced total cell numbers, supporting a role of Alk3 as mediator of LC differentiation and proliferation. Conversely Alk3DCD11c mice, which lack Alk3 on fully developed DCs, display a normal LC network, indicating that Alk3 is dispensable for network maintenance. However, Alk3DCD11c mice experience a stronger and longer lasting skin inflammation in two different experimental models. LCs from these mice migrate faster with exfiltrating LCs showing stronger expression of MHCII and CD86. Furthermore, we recently observed strong upregulation of BMP-7 and Alk3 signaling in inflamed human psoriatic epidermis. Therefore, we conclude that Alk3 plays an important role in dampening skin inflammation via an LCdependent mechanism. Deeper insight into TGF-b-superfamily signaling in DCs may lead to a better understanding of the mechanisms regulating skin inflammation and might open up new treatment options for diseases like psoriasis.
The role of the galanin system in psoriasis-like skin inflammation F Locker1, S Vidali1, B Holub1,2, J Stockinger1, A Koller1, S Brunner1, D Schwarzenbacher1, R Lang2 and B Kofler1 1 Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria and 2 Department of Dermatology, Paracelsus Medical University, Salzburg, Austria Galanin (GAL) has been shown to be a vasoactive (neuro)-peptide which plays a role in a range of inflammatory diseases. The effects of GAL are mediated via three G protein-coupled receptors (GAL1-3). The aim of the present study was to elucidate which galanin receptor is expressed by endothelial cells and which function this receptor plays in the progression of psoriasis in vitro and in vivo. Healthy and psoriatric human skin was analyzed for expression of GAL1-3 by immunohistochemistry. Psoriasis-like skin inflammation was induced via daily topical application of 5% imiquimod (IMQ) (Aldara) on the shaved and depilated back skin of 8-10 week old male and female GAL2-knockout (KO) and GAL3-KO mice for 6 consecutive days. In healthy human skin GAL3 staining was observed around large, mature vessels. In psoriatric skin GAL3 staining was also observed in large, mature vessels. In addition, in newly formed micro-vessels GAL3 staining co-localized with nestin, a marker of neovascularization. Psoriasis development in skin of GAL3-KO animals resulted in a significant lower psoriasis disease severity score, mRNA levels of IL-17A, IL-22, IL-23 and TNF-a and reduced density of CD31 positive vessels compared to wild types on day 4. Neutrophil derived myeloperoxidase activity was significantly lowered in GAL3-KO mice compared to WT mice which was in line with reduced neutrophil infiltration in psoriatric skin of GAL3-KO mice. The total number of macrophages and mast cells in the skin was not affected by lack of GAL3. GAL2-KO mice did not differ significantly from WT mice at both the macroscopic and molecular levels in their inflammatory response to IMQ treatment. Our data indicate that GAL3, but not GAL2, plays an important role in neovascularization and psoriasis-like skin inflammation.
www.jidonline.org S253