Imperial College London

ProfessorMarinaBotto

Faculty of MedicineDepartment of Medicine

Director of Bioservices, Professor of Rheumatology
 
 
 
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Contact

 

+44 (0)20 3313 2316m.botto Website

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N10Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

191 results found

Cortini A, Ellinghaus U, Malik TH, Cunninghame Graham DS, Botto M, Vyse TJet al., 2017, B cell OX40L supports T follicular helper cell development and contributes to SLE pathogenesis., Ann Rheum Dis

OBJECTIVES: TNFSF4 (encodes OX40L) is a susceptibility locus for systemic lupus erythematosus (SLE). Risk alleles increase TNFSF4 expression in cell lines, but the mechanism linking this effect to disease is unclear, and the OX40L-expressing cell types mediating the risk are not clearly established. Blockade of OX40L has been demonstrated to reduce disease severity in several models of autoimmunity, but not in SLE. We sought to investigate its potential therapeutic role in lupus. METHODS: We used a conditional knockout mouse system to investigate the function of OX40L on B and T lymphocytes in systemic autoimmunity. RESULTS: Physiologically, OX40L on both B and T cells contributed to the humoral immune response, but B cell OX40L supported the secondary humoral response and antibody affinity maturation. Our data also indicated that loss of B cell OX40L impeded the generation of splenic T follicular helper cells. We further show that in two models of SLE-a spontaneous congenic model and the H2-IA(bm12) graft-versus-host-induced model-loss of B cell OX40L ameliorates the autoimmune phenotype. This improvement was, in each case, accompanied by a decline in T follicular helper cell numbers. Importantly, the germline knockout did not exhibit a markedly different phenotype from the B cell knockout in these models. CONCLUSIONS: These findings contribute to a model in which genetically determined increased OX40L expression promotes human SLE by several mechanisms, contingent on its cellular expression. The improvement in pathology in two models of systemic autoimmunity indicates that OX40L is an excellent therapeutic target in SLE.

JOURNAL ARTICLE

Giacomassi C, Buang N, Ling GS, Crawford G, Cook HT, Scott D, Dazzi F, Strid J, Botto Met al., 2017, Complement C3 Exacerbates Imiquimod-Induced Skin Inflammation and Psoriasiform Dermatitis, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 137, Pages: 760-763, ISSN: 0022-202X

JOURNAL ARTICLE

Kiriakidis S, Hoer SS, Burrows N, Biddlecome G, Khan MN, Thinnes CC, Schofield CJ, Rogers N, Botto M, Paleolog E, Maxwell PHet al., 2017, Complement C1q is hydroxylated by collagen prolyl 4 hydroxylase and is sensitive to off-target inhibition by prolyl hydroxylase domain inhibitors that stabilize hypoxia-inducible factor, KIDNEY INTERNATIONAL, Vol: 92, Pages: 900-908, ISSN: 0085-2538

JOURNAL ARTICLE

Lynskey NN, Reglinski M, Calay D, Siggins MK, Mason JC, Botto M, Sriskandan Set al., 2017, Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase, PLOS PATHOGENS, Vol: 13, ISSN: 1553-7366

JOURNAL ARTICLE

Muehlfeld C, Madsen J, Mackay R-M, Schneider JP, Schipke J, Lutz D, Birkelbach B, Knudsen L, Botto M, Ochs M, Clark Het al., 2017, Effect of irradiation/bone marrow transplantation on alveolar epithelial type II cells is aggravated in surfactant protein D deficient mice, HISTOCHEMISTRY AND CELL BIOLOGY, Vol: 147, Pages: 49-61, ISSN: 0948-6143

JOURNAL ARTICLE

Stratigou V, Doyle AF, Carlucci F, Stephens L, Foschi V, Castelli M, McKenna N, Cook HT, Lightstone L, Cairns TD, Pickering MC, Botto Met al., 2017, Altered expression of signalling lymphocyte activation molecule receptors in T-cells from lupus nephritis patients-a potential biomarker of disease activity, RHEUMATOLOGY, Vol: 56, Pages: 1206-1216, ISSN: 1462-0324

JOURNAL ARTICLE

Barbour TD, Ling GS, Ruseva MM, Fossati-Jimack L, Cook HT, Botto M, Pickering MCet al., 2016, Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy, KIDNEY INTERNATIONAL, Vol: 89, Pages: 823-832, ISSN: 0085-2538

JOURNAL ARTICLE

Bulla R, Tripodo C, Rami D, Ling GS, Agostinis C, Guarnotta C, Zorzet S, Durigutto P, Botto M, Tedesco Fet al., 2016, C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723

JOURNAL ARTICLE

Carlucci F, Ishaque A, Ling GS, Szajna M, Sandison A, Donatien P, Cook HT, Botto Met al., 2016, C1q Modulates the Response to TLR7 Stimulation by Pristane-Primed Macrophages: Implications for Pristane-Induced Lupus, JOURNAL OF IMMUNOLOGY, Vol: 196, Pages: 1488-1494, ISSN: 0022-1767

JOURNAL ARTICLE

Scott D, Botto M, 2016, The paradoxical roles of C1q and C3 in autoimmunity., Immunobiology, Vol: 221, Pages: 719-725

In this review we will focus on the links between complement and autoimmune diseases and will highlight how animal models have provided insights into the manner by which C1q and C3 act to modulate both adaptive and innate immune responses. In particular we will highlight how C1q may not only act as initiator of the classical complement pathway, but can also mediate multiple immune responses in a complement activation independent manner.

JOURNAL ARTICLE

Vernon KA, Ruseva MM, Cook HT, Botto M, Malik TH, Pickering MCet al., 2016, Partial Complement Factor H Deficiency Associates with C3 Glomerulopathy and Thrombotic Microangiopathy, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 27, Pages: 1334-1342, ISSN: 1046-6673

JOURNAL ARTICLE

Wang Y, Jenkins SA, Gu C, Shree A, Martinez-Moczygemba M, Herold J, Botto M, Wetsel RA, Xu Yet al., 2016, Bacillus anthracis Spore Surface Protein BclA Mediates Complement Factor H Binding to Spores and Promotes Spore Persistence, PLOS PATHOGENS, Vol: 12, ISSN: 1553-7366

JOURNAL ARTICLE

Ambrose N, Khan E, Ravindran R, Lightstone L, Abraham S, Botto M, Johns M, Haskard DOet al., 2015, The exaggerated inflammatory response in Behcet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-gamma/CXCL10 IP-10 pathway, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 181, Pages: 427-433, ISSN: 0009-9104

JOURNAL ARTICLE

Clarke AJ, Ellinghaus U, Cortini A, Stranks A, Simon AK, Botto M, Vyse TJet al., 2015, Autophagy is activated in systemic lupus erythematosus and required for plasmablast development, ANNALS OF THE RHEUMATIC DISEASES, Vol: 74, Pages: 912-920, ISSN: 0003-4967

JOURNAL ARTICLE

Fossati-Jimack L, Ling GS, Baudino L, Szajna M, Manivannan K, Zhao JC, Midgley R, Chai J-G, Simpson E, Botto M, Scott Det al., 2015, Intranasal peptide-induced tolerance and linked suppression: consequences of complement deficiency, IMMUNOLOGY, Vol: 144, Pages: 149-157, ISSN: 0019-2805

JOURNAL ARTICLE

Karpus ON, Kiener HP, Niederreiter B, Yilmaz-Elis AS, van der Kaa J, Ramaglia V, Arens R, Smolen JS, Botto M, Tak PP, Verbeek JS, Hamann Jet al., 2015, CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis, ARTHRITIS RESEARCH & THERAPY, Vol: 17, ISSN: 1478-6354

JOURNAL ARTICLE

Pekkarinen PT, Heikkila N, Kisand K, Peterson P, Botto M, Daha MR, Drouet C, Isaac L, Helminen M, Haahtela T, Meri S, Jarva H, Arstila TPet al., 2015, Dysregulation of adaptive immune responses in complement C3-deficient patients, EUROPEAN JOURNAL OF IMMUNOLOGY, Vol: 45, Pages: 915-921, ISSN: 0014-2980

JOURNAL ARTICLE

Saja MF, Baudino L, Jackson WD, Cook HT, Malik TH, Fossati-Jimack L, Ruseva M, Pickering MC, Woollard KJ, Botto Met al., 2015, Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes, CELL REPORTS, Vol: 12, Pages: 1802-1815, ISSN: 2211-1247

JOURNAL ARTICLE

Sumida T, Naito AT, Nomura S, Nakagawa A, Higo T, Hashimoto A, Okada K, Sakai T, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee J-K, Minamino T, Offermanns S, Noda T, Botto M, Kobayashi Y, Morita H, Manabe I, Nagai T, Shiojima I, Komuro Iet al., 2015, Complement C1q-induced activation of beta-catenin signalling causes hypertensive arterial remodelling, NATURE COMMUNICATIONS, Vol: 6, ISSN: 2041-1723

JOURNAL ARTICLE

Banda NK, Mehta G, Chao Y, Wang G, Inturi S, Fossati-Jimack L, Botto M, Wu L, Moghimi SM, Simberg Det al., 2014, Mechanisms of complement activation by dextran-coated superparamagnetic iron oxide (SPIO) nanoworms in mouse versus human serum, PARTICLE AND FIBRE TOXICOLOGY, Vol: 11, ISSN: 1743-8977

JOURNAL ARTICLE

Baudino L, Sardini A, Ruseva MM, Fossati-Jimack L, Cook HT, Scott D, Simpson E, Botto Met al., 2014, C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 111, Pages: 1503-1508, ISSN: 0027-8424

JOURNAL ARTICLE

Bossi F, Tripodo C, Rizzi L, Bulla R, Agostinis C, Guarnotta C, Munaut C, Baldassarre G, Papa G, Zorzet S, Ghebrehiwet B, Ling GS, Botto M, Tedesco Fet al., 2014, C1q as a unique player in angiogenesis with therapeutic implication in wound healing, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 111, Pages: 4209-4214, ISSN: 0027-8424

JOURNAL ARTICLE

Giacomassi C, Ling GS, Strid J, Dazzi F, Botto Met al., 2014, Complement C3 exacerbates skin inflammation in a murine model of imiquimod-induced psoriasis, IMMUNOLOGY, Vol: 143, Pages: 120-120, ISSN: 0019-2805

JOURNAL ARTICLE

Ling GS, Bennett J, Woollard KJ, Szajna M, Fossati-Jimack L, Taylor PR, Scott D, Franzoso G, Cook HT, Botto Met al., 2014, Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723

JOURNAL ARTICLE

Sattler S, Ling G-S, Xu D, Hussaarts L, Romaine A, Zhao H, Fossati-Jimack L, Malik T, Cook HT, Botto M, Lau Y-L, Smits HH, Liew FY, Huang F-Pet al., 2014, IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut, JOURNAL OF AUTOIMMUNITY, Vol: 50, Pages: 107-122, ISSN: 0896-8411

JOURNAL ARTICLE

Fossati-Jimack L, Ling GS, Cortini A, Szajna M, Malik TH, McDonald JU, Pickering MC, Cook HT, Taylor PR, Botto Met al., 2013, Phagocytosis Is the Main CR3-Mediated Function Affected by the Lupus-Associated Variant of CD11b in Human Myeloid Cells, PLOS ONE, Vol: 8, ISSN: 1932-6203

JOURNAL ARTICLE

Kraivong R, Vasanawathana S, Limpitikul W, Malasit P, Tangthawornchaikul N, Botto M, Screaton GR, Mongkolsapaya J, Pickering MCet al., 2013, Complement alternative pathway genetic variation and Dengue infection in the Thai population, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 174, Pages: 326-334, ISSN: 0009-9104

JOURNAL ARTICLE

Ruseva MM, Vernon KA, Lesher AM, Schwaeble WJ, Ali YM, Botto M, Cook T, Song W, Stover CM, Pickering MCet al., 2013, Loss of Properdin Exacerbates C3 Glomerulopathy Resulting from Factor H Deficiency, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 24, Pages: 43-52, ISSN: 1046-6673

JOURNAL ARTICLE

Humphries MM, Kenna PF, Campbell M, Tam LCS, Nguyen ATH, Farrar GJ, Botto M, Kiang AS, Humphries Pet al., 2012, C1q enhances cone photoreceptor survival in a mouse model of autosomal recessive retinitis pigmentosa, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 20, Pages: 64-68, ISSN: 1018-4813

JOURNAL ARTICLE

Lewis MJ, Malik TH, Fossati-Jimack L, Carassiti D, Cook HT, Haskard DO, Botto Met al., 2012, Distinct roles for complement in glomerulonephritis and atherosclerosis revealed in mice with a combination of lupus and hyperlipidemia, ARTHRITIS AND RHEUMATISM, Vol: 64, Pages: 2707-2718, ISSN: 0004-3591

JOURNAL ARTICLE

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