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Article ; Online: Obesity can turn a therapy into an antitherapy in atopic dermatitis.

Cook, Emma C L / Redondo-Urzainqui, Ana / Iborra, Salvador

2022 Volume 77, Issue 11, Page(s) 3473–3475

MeSH term(s)	Humans ; Dermatitis, Atopic/drug therapy ; Obesity/complications
Language	English
Publishing date	2022-08-25
Publishing country	Denmark
Document type	News ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15482
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Article ; Online: Dendritic cells in energy balance regulation.

Redondo-Urzainqui, Ana / Hernández-García, Elena / Cook, Emma Clare Laura / Iborra, Salvador

Immunology letters

2022 Volume 253, Page(s) 19–27

Abstract: Besides their well-known role in initiating adaptive immune responses, several groups have studied the role of dendritic cells (DCs) in the context of chronic metabolic inflammation, such as in diet-induced obesity (DIO) or metabolic-associated fatty ... ...

Abstract	Besides their well-known role in initiating adaptive immune responses, several groups have studied the role of dendritic cells (DCs) in the context of chronic metabolic inflammation, such as in diet-induced obesity (DIO) or metabolic-associated fatty liver disease. DCs also have an important function in maintaining metabolic tissue homeostasis in steady-state conditions. In this review, we will briefly describe the different DC subsets, the murine models available to assess their function, and discuss the role of DCs in regulating energy balance and maintaining tissue homeostasis.
MeSH term(s)	Mice ; Animals ; Inflammation/metabolism ; Homeostasis ; Obesity ; Dendritic Cells ; Immunity, Humoral
Language	English
Publishing date	2022-12-29
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	445150-8
ISSN	1879-0542 ; 0165-2478
ISSN (online)	1879-0542
ISSN	0165-2478
DOI	10.1016/j.imlet.2022.12.002
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Article ; Online: Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus.

Muñoz-Callejas, Antonio / González-Sánchez, Elena / Silván, Javier / San Antonio, Esther / González-Tajuelo, Rafael / Ramos-Manzano, Alejandra / Sánchez-Abad, Inés / González-Alvaro, Isidoro / García-Pérez, Javier / Tomero, Eva G / de Vicuña, Rosario García / Vicente-Rabaneda, Esther F / Castañeda, Santos / Urzainqui, Ana

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the generation of anti-DNA autoantibodies due to exposure of immune cells to excessive amounts of extracellular DNA. Lack of P-selectin in mice induces the development of a ... ...

Abstract	Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the generation of anti-DNA autoantibodies due to exposure of immune cells to excessive amounts of extracellular DNA. Lack of P-selectin in mice induces the development of a lupus-like syndrome and patients with cutaneous lupus have reduced P-selectin expression in skin vessels. Using flow cytometry we analyzed in healthy donors and patients the expression of P-selectin Glycoprotein Ligand-1 (PSGL-1) in circulating neutrophils and the implication of PSGL-1/P-selectin interaction in neutrophil extracellular traps (NETs) generation. We found a statistical significance that neutrophils from active SLE patients have a reduced expression of PSGL-1 and low levels of PSGL-1 in neutrophils from SLE patients associated with the presence of anti-dsDNA antibodies, clinical lung involvement, Raynaud's phenomenon, and positive lupus anticoagulant. PSGL-1 is present along the DNA in the NET. In healthy donors, neutrophil interaction with immobilized P-selectin triggers Syk activation, increases the NETs percentage and reduces the amount of DNA extruded in the NETs. In active SLE patients, neutrophil interaction with P-selectin does not activate Syk or reduce the amount of DNA extruded in the NETs, that might contribute to increase the extracellular level of DNA and hence, to disease pathogenesis.
MeSH term(s)	Animals ; Mice ; Autoimmune Diseases/metabolism ; DNA/metabolism ; Extracellular Traps/metabolism ; Lupus Erythematosus, Systemic ; Neutrophils/metabolism ; P-Selectin/metabolism ; Humans
Chemical Substances	DNA (9007-49-2) ; P-Selectin ; P-selectin ligand protein
Language	English
Publishing date	2023-03-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076144
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Article ; Online: Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity.

Hernández-García, Elena / Cueto, Francisco J / Cook, Emma C L / Redondo-Urzainqui, Ana / Charro-Zanca, Sara / Robles-Vera, Iñaki / Conde-Garrosa, Ruth / Nikolić, Ivana / Sabio, Guadalupe / Sancho, David / Iborra, Salvador

Cellular & molecular immunology

2022 Volume 19, Issue 2, Page(s) 260–275

Abstract: Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, ... ...

Abstract	Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, we showed that Batf3-deficient mice lacking conventional type 1 DCs (cDC1s) had increased body weight and adiposity during aging. This led to impaired energy expenditure and glucose tolerance, insulin resistance, dyslipidemia, and liver steatosis. cDC1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1
MeSH term(s)	Adipose Tissue ; Animals ; Dendritic Cells ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Natural Killer T-Cells ; Obesity
Language	English
Publishing date	2022-01-04
Publishing country	China
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2435097-7
ISSN	2042-0226 ; 1672-7681
ISSN (online)	2042-0226
ISSN	1672-7681
DOI	10.1038/s41423-021-00812-7
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Article ; Online: Beneficial effect of temporary methotrexate interruption on B and T cell responses upon SARS-CoV-2 vaccination in patients with rheumatoid arthritis or psoriatic arthritis.

Martínez-Fleta, Pedro / Vicente-Rabaneda, Esther F / Triguero-Martínez, Ana / Roy-Vallejo, Emilia / Uriarte-Ecenarro, Miren / Gutiérrez-Rodríguez, Francisco / Quiroga-Colina, Patricia / Romero-Robles, Ana / Montes, Nuria / García-Castañeda, Noelia / Mejía-Abril, Gina P / García-Vadillo, Jesús A / Llorente-Cubas, Irene / Villagrasa, José R / Serra López-Matencio, José M / Ancochea, Julio / Urzainqui, Ana / Esparcia-Pinedo, Laura / Alfranca, Arantzazu /

de la Fuente, Hortensia / García-Vicuña, Rosario / Sánchez-Madrid, Francisco / González-Álvaro, Isidoro / Castañeda, Santos

NPJ vaccines

2024 Volume 9, Issue 1, Page(s) 21

Abstract: B and T cell responses were evaluated in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) after 1 or 2 weeks of methotrexate (MTX) withdrawal following each COVID-19 vaccine dose and compared with those who maintained MTX. Adult RA ... ...

Abstract	B and T cell responses were evaluated in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) after 1 or 2 weeks of methotrexate (MTX) withdrawal following each COVID-19 vaccine dose and compared with those who maintained MTX. Adult RA and PsA patients treated with MTX were recruited and randomly assigned to 3 groups: MTX-maintenance (n = 72), MTX-withdrawal for 1 week (n = 71) or MTX-withdrawal for 2 weeks (n = 73). Specific antibodies to several SARS-CoV-2 antigens and interferon (IFN)-γ and interleukin (IL)-21 responses were assessed. MTX withdrawal in patients without previous COVID-19 was associated with higher levels of anti-RBD IgG and neutralising antibodies, especially in the 2-week withdrawal group and with higher IFN-γ secretion upon stimulation with pools of SARS-CoV-2 S peptides. No increment of RA/PsA relapses was detected across groups. Our data indicate that two-week MTX interruption following COVID-19 vaccination in patients with RA or PsA improves humoral and cellular immune responses.
Language	English
Publishing date	2024-01-30
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-024-00805-3
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Article ; Online: Resistance to Experimental Visceral Leishmaniasis in Mice Infected With

Soto, Manuel / Ramírez, Laura / Solana, José Carlos / Cook, Emma C L / Hernández-García, Elena / Charro-Zanca, Sara / Redondo-Urzainqui, Ana / Reguera, Rosa M / Balaña-Fouce, Rafael / Iborra, Salvador

Frontiers in immunology

2020 Volume 11, Page(s) 590934

Abstract: Unveiling the protective immune response to visceral leishmaniasis is critical for a rational design of vaccines aimed at reducing the impact caused by this fatal, if left untreated, vector-borne disease. In this study we sought to determine the role of ... ...

Abstract	Unveiling the protective immune response to visceral leishmaniasis is critical for a rational design of vaccines aimed at reducing the impact caused by this fatal, if left untreated, vector-borne disease. In this study we sought to determine the role of the basic leucine zipper transcription factor ATF-like 3 (Batf3) in the evolution of infection with
Language	English
Publishing date	2020-12-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.590934
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Article ; Online: Relevance of PSGL-1 Expression in B Cell Development and Activation.

González-Tajuelo, Rafael / González-Sánchez, Elena / Silván, Javier / Muñoz-Callejas, Antonio / Vicente-Rabaneda, Esther / García-Pérez, Javier / Castañeda, Santos / Urzainqui, Ana

Frontiers in immunology

2020 Volume 11, Page(s) 588212

Abstract: PSGL-1 is expressed in all plasma cells, but only in a small percentage of circulating B cells. Patients with systemic sclerosis (SSc) show reduced expression of PSGL-1 in B cells and increased prevalence of pulmonary arterial hypertension. PSGL-1 ... ...

Abstract	PSGL-1 is expressed in all plasma cells, but only in a small percentage of circulating B cells. Patients with systemic sclerosis (SSc) show reduced expression of PSGL-1 in B cells and increased prevalence of pulmonary arterial hypertension. PSGL-1 deficiency leads to a SSc-like syndrome and SSc-associated pulmonary hypertension in female mice. In this work, the expression of PSGL-1 was assessed during murine B cell development in the bone marrow and in several peripheral and spleen B cell subsets. The impact of PSGL-1 absence on B cell biology was also evaluated. Interestingly, the percentage of PSGL-1 expressing cells and PSGL-1 expression levels decreased in the transition from common lymphoid progenitors to immature B cells.
MeSH term(s)	Aged ; Animals ; B-Lymphocytes/immunology ; Female ; Humans ; Male ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Peritoneal Cavity/cytology ; Pulmonary Arterial Hypertension/immunology ; Spleen/cytology ; Spleen/immunology
Chemical Substances	Membrane Glycoproteins ; P-selectin ligand protein
Language	English
Publishing date	2020-11-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.588212
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Article ; Online: Targeted nanotherapy with everolimus reduces inflammation and fibrosis in scleroderma-related interstitial lung disease developed by PSGL-1 deficient mice.

González-Sánchez, Elena / Muñoz-Callejas, Antonio / Gómez-Román, Javier / San Antonio, Esther / Marengo, Alessandro / Tsapis, Nicolas / Bohne-Japiassu, Kamila / González-Tajuelo, Rafael / Pereda, Saray / García-Pérez, Javier / Cavagna, Lorenzo / González-Gay, Miguel Ángel / Vicente-Rabaneda, Esther Francisca / Meloni, Federica / Fattal, Elias / Castañeda, Santos / Urzainqui, Ana

British journal of pharmacology

2022 Volume 179, Issue 18, Page(s) 4534–4548

Abstract: Background and purpose: Interstitial lung disease (ILD) is the main cause of mortality in systemic sclerosis (SSc), and current therapies available are of low efficacy or high toxicity. Thus, the identification of innovative less toxic and high efficacy ...

Abstract	Background and purpose: Interstitial lung disease (ILD) is the main cause of mortality in systemic sclerosis (SSc), and current therapies available are of low efficacy or high toxicity. Thus, the identification of innovative less toxic and high efficacy therapeutic approaches to ILD treatment is an urgent need. The interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin initiates leukocyte extravasation and deletion of the corresponding gene (Selplg) induces a SSc-like syndrome with high incidence of ILD in aged mice. Experimental approach: Aged PSGL-1 KO (Selplg Key results: PSGL-1 KO mice had increased numbers of CD45+ and CD45- cells, including alveolar and interstitial macrophages, eosinophils, granulocytes and NK cells, and myofibroblasts in bronchoalveolar lavage (BAL). CD45+ and CD45- cells expressing pro-inflammatory and pro-fibrotic cytokines were also increased. Lungs from PSGL-1 KO mice showed increased immune cell infiltration and apoptosis and exacerbated interstitial and peribronchial fibrosis. Targeted nanotherapy with LipHA+Ev decreased the myofibroblasts in BAL, cells producing proinflammatory and profibrotic cytokines, and the degree of lung inflammation at histology. LipHA+Ev treatment also decreased the severity of peribronchial and interstitial lung fibrosis, from moderate to mild levels. Conclusions and implications: In PSGL-1 KO mice, targeted nanotherapy with LipHA+Ev was an effective treatment for SSc-ILD, reducing the number of inflammatory and fibrotic cells in BAL and reducing inflammation and fibrosis in lungs.
MeSH term(s)	Animals ; Cytokines ; Everolimus/pharmacology ; Everolimus/therapeutic use ; Fibrosis ; Inflammation/pathology ; Lung/pathology ; Lung Diseases, Interstitial/drug therapy ; Lung Diseases, Interstitial/etiology ; Membrane Glycoproteins ; Mice ; Pulmonary Fibrosis/drug therapy ; Pulmonary Fibrosis/genetics ; Scleroderma, Systemic/pathology
Chemical Substances	Cytokines ; Membrane Glycoproteins ; P-selectin ligand protein ; Everolimus (9HW64Q8G6G)
Language	English
Publishing date	2022-07-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15898
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Article ; Online: Endothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis.

Esteban, Sergio / Clemente, Cristina / Koziol, Agnieszka / Gonzalo, Pilar / Rius, Cristina / Martínez, Fernando / Linares, Pablo M / Chaparro, María / Urzainqui, Ana / Andrés, Vicente / Seiki, Motoharu / Gisbert, Javier P / Arroyo, Alicia G

EMBO molecular medicine

2019 Volume 12, Issue 2, Page(s) e10862

Abstract: Pathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood ... ...

Abstract	Pathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood flow and splitting of pre-existing capillaries. In this report, mice lacking the protease MT1-MMP in endothelial cells (MT1
MeSH term(s)	Animals ; Colitis/metabolism ; Colitis/pathology ; Endothelial Cells ; Humans ; Intussusception ; Matrix Metalloproteinase 14/metabolism ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; Nitric Oxide/metabolism ; Thrombospondin 1/metabolism
Chemical Substances	Thrombospondin 1 ; Nitric Oxide (31C4KY9ESH) ; Matrix Metalloproteinase 14 (EC 3.4.24.80)
Language	English
Publishing date	2019-12-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.201910862
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Article ; Online: Deregulated PSGL-1 Expression in B Cells and Dendritic Cells May Be Implicated in Human Systemic Sclerosis Development.

Silván, Javier / González-Tajuelo, Rafael / Vicente-Rabaneda, Esther / Pérez-Frías, Alicia / Espartero-Santos, Marina / Muñoz-Callejas, Antonio / García-Lorenzo, Elena / Gamallo, Carlos / Castañeda, Santos / Urzainqui, Ana

The Journal of investigative dermatology

2018 Volume 138, Issue 10, Page(s) 2123–2132

Abstract: Systemic sclerosis (SSc) is an autoimmune disorder with high morbidity and mortality, is difficult to diagnose early, and has no curative treatment. PSGL-1 is a leukocyte receptor whose deficiency in mice promotes an SSc-like disease. ADAM8, a ... ...

Abstract	Systemic sclerosis (SSc) is an autoimmune disorder with high morbidity and mortality, is difficult to diagnose early, and has no curative treatment. PSGL-1 is a leukocyte receptor whose deficiency in mice promotes an SSc-like disease. ADAM8, a metalloprotease that cleaves PSGL-1, is implicated in inflammatory processes. Our goal was to evaluate whether PSGL-1 and ADAM8 contribute to the pathogenesis of human SSc. We found that patients with SSc presented increased PSGL-1 expression on monocytes, dendritic cells, and T cells and decreased expression of PSGL-1 on B cells. PSGL-1 on monocytes from SSc patients failed to induce Syk phosphorylation or IL-10 production after interaction with P-selectin. Up to 60% of the IL-10-producing B cells expressed PSGL-1, pointing to a regulatory role for PSGL-1 in B cells, and PSGL-1
MeSH term(s)	ADAM Proteins/biosynthesis ; Adult ; Aged ; Aged, 80 and over ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Down-Regulation/physiology ; Female ; Humans ; Male ; Membrane Glycoproteins/biosynthesis ; Membrane Proteins/biosynthesis ; Middle Aged ; Scleroderma, Systemic/immunology ; Scleroderma, Systemic/metabolism ; Scleroderma, Systemic/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/pathology ; Young Adult
Chemical Substances	Membrane Glycoproteins ; Membrane Proteins ; P-selectin ligand protein ; ADAM Proteins (EC 3.4.24.-) ; ADAM8 protein, human (EC 3.4.24.-)
Language	English
Publishing date	2018-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2018.04.003
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