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Genetic Variants Predisposing Most Strongly to Type 1 Diabetes Diagnosed Under Age 7 Years Lie Near Candidate Genes That Function in the Immune System and in Pancreatic β-Cells.

Inshaw JRJ, Cutler AJ, Crouch DJM, Wicker LS, Todd JA.

Diabetes Care. 2019 Sep 26. pii: dc190803. doi: 10.2337/dc19-0803. [Epub ahead of print]


Stochastic search and joint fine-mapping increases accuracy and identifies previously unreported associations in immune-mediated diseases.

Asimit JL, Rainbow DB, Fortune MD, Grinberg NF, Wicker LS, Wallace C.

Nat Commun. 2019 Jul 19;10(1):3216. doi: 10.1038/s41467-019-11271-0.


Genetic and functional data identifying Cd101 as a type 1 diabetes (T1D) susceptibility gene in nonobese diabetic (NOD) mice.

Mattner J, Mohammed JP, Fusakio ME, Giessler C, Hackstein CP, Opoka R, Wrage M, Schey R, Clark J, Fraser HI, Rainbow DB, Wicker LS.

PLoS Genet. 2019 Jun 14;15(6):e1008178. doi: 10.1371/journal.pgen.1008178. eCollection 2019 Jun.


A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease.

Peterson LB, Bell CJM, Howlett SK, Pekalski ML, Brady K, Hinton H, Sauter D, Todd JA, Umana P, Ast O, Waldhauer I, Freimoser-Grundschober A, Moessner E, Klein C, Hosse RJ, Wicker LS.

J Autoimmun. 2018 Dec;95:1-14. doi: 10.1016/j.jaut.2018.10.017. Epub 2018 Nov 13.


The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in patients with type 1 diabetes.

Seelig E, Howlett J, Porter L, Truman L, Heywood J, Kennet J, Arbon EL, Anselmiova K, Walker NM, Atkar R, Pekalski ML, Rytina E, Evans M, Wicker LS, Todd JA, Mander AP, Bond S, Waldron-Lynch F.

JCI Insight. 2018 Oct 4;3(19). pii: 99306. doi: 10.1172/jci.insight.99306.


The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus.

Oliveira JJ, Karrar S, Rainbow DB, Pinder CL, Clarke P, Rubio García A, Al-Assar O, Burling K, Morris S, Stratton R, Vyse TJ, Wicker LS, Todd JA, Ferreira RC.

Arthritis Res Ther. 2018 Jul 27;20(1):152. doi: 10.1186/s13075-018-1649-1.


A Novel Pkhd1 Mutation Interacts with the Nonobese Diabetic Genetic Background To Cause Autoimmune Cholangitis.

Huang W, Rainbow DB, Wu Y, Adams D, Shivakumar P, Kottyan L, Karns R, Aronow B, Bezerra J, Gershwin ME, Peterson LB, Wicker LS, Ridgway WM.

J Immunol. 2018 Jan 1;200(1):147-162. doi: 10.4049/jimmunol.1701087. Epub 2017 Nov 20.


Chromosome contacts in activated T cells identify autoimmune disease candidate genes.

Burren OS, Rubio García A, Javierre BM, Rainbow DB, Cairns J, Cooper NJ, Lambourne JJ, Schofield E, Castro Dopico X, Ferreira RC, Coulson R, Burden F, Rowlston SP, Downes K, Wingett SW, Frontini M, Ouwehand WH, Fraser P, Spivakov M, Todd JA, Wicker LS, Cutler AJ, Wallace C.

Genome Biol. 2017 Sep 4;18(1):165. doi: 10.1186/s13059-017-1285-0.


Capturing the systemic immune signature of a norovirus infection: an n-of-1 case study within a clinical trial.

Cutler AJ, Oliveira J, Ferreira RC, Challis B, Walker NM, Caddy S, Lu J, Stevens HE, Smyth DJ, Pekalski ML, Kennet J, Hunter KMD, Goodfellow I, Wicker LS, Todd JA, Waldron-Lynch F.

Wellcome Open Res. 2017 Oct 5;2:28. doi: 10.12688/wellcomeopenres.11300.3. eCollection 2017.


Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2.

Pekalski ML, García AR, Ferreira RC, Rainbow DB, Smyth DJ, Mashar M, Brady J, Savinykh N, Dopico XC, Mahmood S, Duley S, Stevens HE, Walker NM, Cutler AJ, Waldron-Lynch F, Dunger DB, Shannon-Lowe C, Coles AJ, Jones JL, Wallace C, Todd JA, Wicker LS.

JCI Insight. 2017 Aug 17;2(16). pii: 93739. doi: 10.1172/jci.insight.93739. eCollection 2017 Aug 17.


Cells with Treg-specific FOXP3 demethylation but low CD25 are prevalent in autoimmunity.

Ferreira RC, Simons HZ, Thompson WS, Rainbow DB, Yang X, Cutler AJ, Oliveira J, Castro Dopico X, Smyth DJ, Savinykh N, Mashar M, Vyse TJ, Dunger DB, Baxendale H, Chandra A, Wallace C, Todd JA, Wicker LS, Pekalski ML.

J Autoimmun. 2017 Nov;84:75-86. doi: 10.1016/j.jaut.2017.07.009. Epub 2017 Jul 23.


In-depth immunophenotyping data of IL-6R on the human peripheral regulatory T cell (Treg) compartment.

Ferreira RC, Rainbow DB, Rubio García A, Pekalski ML, Porter L, Oliveira JJ, Waldron-Lynch F, Wicker LS, Todd JA.

Data Brief. 2017 May 2;12:676-691. doi: 10.1016/j.dib.2017.04.043. eCollection 2017 Jun.


Human IL-6RhiTIGIT- CD4+CD127lowCD25+ T cells display potent in vitro suppressive capacity and a distinct Th17 profile.

Ferreira RC, Rainbow DB, Rubio García A, Pekalski ML, Porter L, Oliveira JJ, Waldron-Lynch F, Wicker LS, Todd JA.

Clin Immunol. 2017 Jun;179:25-39. doi: 10.1016/j.clim.2017.03.002. Epub 2017 Mar 9.


Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.

Todd JA, Evangelou M, Cutler AJ, Pekalski ML, Walker NM, Stevens HE, Porter L, Smyth DJ, Rainbow DB, Ferreira RC, Esposito L, Hunter KM, Loudon K, Irons K, Yang JH, Bell CJ, Schuilenburg H, Heywood J, Challis B, Neupane S, Clarke P, Coleman G, Dawson S, Goymer D, Anselmiova K, Kennet J, Brown J, Caddy SL, Lu J, Greatorex J, Goodfellow I, Wallace C, Tree TI, Evans M, Mander AP, Bond S, Wicker LS, Waldron-Lynch F.

PLoS Med. 2016 Oct 11;13(10):e1002139. doi: 10.1371/journal.pmed.1002139. eCollection 2016 Oct.


Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study.

Truman LA, Pekalski ML, Kareclas P, Evangelou M, Walker NM, Howlett J, Mander AP, Kennet J, Wicker LS, Bond S, Todd JA, Waldron-Lynch F.

BMJ Open. 2015 Dec 8;5(12):e009799. doi: 10.1136/bmjopen-2015-009799.


Ptpn22 and Cd2 Variations Are Associated with Altered Protein Expression and Susceptibility to Type 1 Diabetes in Nonobese Diabetic Mice.

Fraser HI, Howlett S, Clark J, Rainbow DB, Stanford SM, Wu DJ, Hsieh YW, Maine CJ, Christensen M, Kuchroo V, Sherman LA, Podolin PL, Todd JA, Steward CA, Peterson LB, Bottini N, Wicker LS.

J Immunol. 2015 Nov 15;195(10):4841-52. doi: 10.4049/jimmunol.1402654. Epub 2015 Oct 5.


Epigenetic analysis of regulatory T cells using multiplex bisulfite sequencing.

Rainbow DB, Yang X, Burren O, Pekalski ML, Smyth DJ, Klarqvist MD, Penkett CJ, Brugger K, Martin H, Todd JA, Wallace C, Wicker LS.

Eur J Immunol. 2015 Nov;45(11):3200-3. doi: 10.1002/eji.201545646. Epub 2015 Oct 1. No abstract available.


Natural Variation in Interleukin-2 Sensitivity Influences Regulatory T-Cell Frequency and Function in Individuals With Long-standing Type 1 Diabetes.

Yang JH, Cutler AJ, Ferreira RC, Reading JL, Cooper NJ, Wallace C, Clarke P, Smyth DJ, Boyce CS, Gao GJ, Todd JA, Wicker LS, Tree TI.

Diabetes. 2015 Nov;64(11):3891-902. doi: 10.2337/db15-0516. Epub 2015 Jul 29.


Dissection of a Complex Disease Susceptibility Region Using a Bayesian Stochastic Search Approach to Fine Mapping.

Wallace C, Cutler AJ, Pontikos N, Pekalski ML, Burren OS, Cooper JD, García AR, Ferreira RC, Guo H, Walker NM, Smyth DJ, Rich SS, Onengut-Gumuscu S, Sawcer SJ, Ban M, Richardson S, Todd JA, Wicker LS.

PLoS Genet. 2015 Jun 24;11(6):e1005272. doi: 10.1371/journal.pgen.1005272. eCollection 2015 Jun.


Genome-wide transcriptional analyses of islet-specific CD4+ T cells identify Idd9 genes controlling diabetogenic T cell function.

Berry GJ, Frielle C, Luu T, Salzberg AC, Rainbow DB, Wicker LS, Waldner H.

J Immunol. 2015 Mar 15;194(6):2654-63. doi: 10.4049/jimmunol.1401288. Epub 2015 Feb 11.


IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients.

Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML.

Diabetologia. 2015 Apr;58(4):781-90. doi: 10.1007/s00125-015-3509-8. Epub 2015 Feb 6.


Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells.

Bell CJ, Sun Y, Nowak UM, Clark J, Howlett S, Pekalski ML, Yang X, Ast O, Waldhauer I, Freimoser-Grundschober A, Moessner E, Umana P, Klein C, Hosse RJ, Wicker LS, Peterson LB.

J Autoimmun. 2015 Jan;56:66-80. doi: 10.1016/j.jaut.2014.10.002. Epub 2014 Oct 30.


Genetic analysis of autoimmune type 1 diabetes mellitus in mice. 1991.

Todd JA, Aitman TJ, Cornall RJ, Ghosh S, Hall JR, Hearne CM, Knight AM, Love JM, McAleer MA, Prins JB, Rodrigues N, Lathrop M, Pressey A, DeLarato NH, Peterson LB, Wicker LS.

J Immunol. 2014 Jul 1;193(1):7-12. No abstract available.


Investigation of soluble and transmembrane CTLA-4 isoforms in serum and microvesicles.

Esposito L, Hunter KM, Clark J, Rainbow DB, Stevens H, Denesha J, Duley S, Dawson S, Coleman G, Nutland S, Bell GL, Moran C, Pekalski M, Todd JA, Wicker LS.

J Immunol. 2014 Jul 15;193(2):889-900. doi: 10.4049/jimmunol.1303389. Epub 2014 Jun 13.


Rationale and study design of the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial.

Waldron-Lynch F, Kareclas P, Irons K, Walker NM, Mander A, Wicker LS, Todd JA, Bond S.

BMJ Open. 2014 Jun 4;4(6):e005559. doi: 10.1136/bmjopen-2014-005559.


Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes.

Thompson WS, Pekalski ML, Simons HZ, Smyth DJ, Castro-Dopico X, Guo H, Guy C, Dunger DB, Arif S, Peakman M, Wallace C, Wicker LS, Todd JA, Ferreira RC.

Clin Exp Immunol. 2014 Sep;177(3):571-85. doi: 10.1111/cei.12362.


Blockade of the programmed death-1 (PD1) pathway undermines potent genetic protection from type 1 diabetes.

Kochupurakkal NM, Kruger AJ, Tripathi S, Zhu B, Adams LT, Rainbow DB, Rossini A, Greiner DL, Sayegh MH, Wicker LS, Guleria I.

PLoS One. 2014 Feb 28;9(2):e89561. doi: 10.1371/journal.pone.0089561. eCollection 2014.


A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes.

Ferreira RC, Guo H, Coulson RM, Smyth DJ, Pekalski ML, Burren OS, Cutler AJ, Doecke JD, Flint S, McKinney EF, Lyons PA, Smith KG, Achenbach P, Beyerlein A, Dunger DB, Clayton DG, Wicker LS, Todd JA, Bonifacio E, Wallace C, Ziegler AG.

Diabetes. 2014 Jul;63(7):2538-50. doi: 10.2337/db13-1777. Epub 2014 Feb 21.


Fine mapping of type 1 diabetes regions Idd9.1 and Idd9.2 reveals genetic complexity.

Hamilton-Williams EE, Rainbow DB, Cheung J, Christensen M, Lyons PA, Peterson LB, Steward CA, Sherman LA, Wicker LS.

Mamm Genome. 2013 Oct;24(9-10):358-75. doi: 10.1007/s00335-013-9466-y. Epub 2013 Aug 11.


The non-obese diabetic mouse sequence, annotation and variation resource: an aid for investigating type 1 diabetes.

Steward CA, Gonzalez JM, Trevanion S, Sheppard D, Kerry G, Gilbert JG, Wicker LS, Rogers J, Harrow JL.

Database (Oxford). 2013 May 31;2013:bat032. doi: 10.1093/database/bat032. Print 2013.


Genetic interactions among Idd3, Idd5.1, Idd5.2, and Idd5.3 protective loci in the nonobese diabetic mouse model of type 1 diabetes.

Lin X, Hamilton-Williams EE, Rainbow DB, Hunter KM, Dai YD, Cheung J, Peterson LB, Wicker LS, Sherman LA.

J Immunol. 2013 Apr 1;190(7):3109-20. doi: 10.4049/jimmunol.1203422. Epub 2013 Feb 20.


Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors.

Pekalski ML, Ferreira RC, Coulson RM, Cutler AJ, Guo H, Smyth DJ, Downes K, Dendrou CA, Castro Dopico X, Esposito L, Coleman G, Stevens HE, Nutland S, Walker NM, Guy C, Dunger DB, Wallace C, Tree TI, Todd JA, Wicker LS.

J Immunol. 2013 Mar 15;190(6):2554-66. doi: 10.4049/jimmunol.1202914. Epub 2013 Feb 15.


The B10 Idd9.3 locus mediates accumulation of functionally superior CD137(+) regulatory T cells in the nonobese diabetic type 1 diabetes model.

Kachapati K, Adams DE, Wu Y, Steward CA, Rainbow DB, Wicker LS, Mittler RS, Ridgway WM.

J Immunol. 2012 Nov 15;189(10):5001-15. doi: 10.4049/jimmunol.1101013. Epub 2012 Oct 12.


PTPN22 alters the development of regulatory T cells in the thymus.

Maine CJ, Hamilton-Williams EE, Cheung J, Stanford SM, Bottini N, Wicker LS, Sherman LA.

J Immunol. 2012 Jun 1;188(11):5267-75. doi: 10.4049/jimmunol.1200150. Epub 2012 Apr 25.


Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function.

Garg G, Tyler JR, Yang JH, Cutler AJ, Downes K, Pekalski M, Bell GL, Nutland S, Peakman M, Todd JA, Wicker LS, Tree TI.

J Immunol. 2012 May 1;188(9):4644-53. doi: 10.4049/jimmunol.1100272. Epub 2012 Mar 28.


Overexpression of the Ctla-4 isoform lacking exons 2 and 3 causes autoimmunity.

Liu SM, Sutherland AP, Zhang Z, Rainbow DB, Quintana FJ, Paterson AM, Sharpe AH, Oukka M, Wicker LS, Kuchroo VK.

J Immunol. 2012 Jan 1;188(1):155-62. doi: 10.4049/jimmunol.1102042. Epub 2011 Nov 28.


Cellular mechanisms of restored β-cell tolerance mediated by protective alleles of Idd3 and Idd5.

Hamilton-Williams EE, Cheung J, Rainbow DB, Hunter KM, Wicker LS, Sherman LA.

Diabetes. 2012 Jan;61(1):166-74. doi: 10.2337/db11-0790. Epub 2011 Nov 21.


Identification of Cd101 as a susceptibility gene for Novosphingobium aromaticivorans-induced liver autoimmunity.

Mohammed JP, Fusakio ME, Rainbow DB, Moule C, Fraser HI, Clark J, Todd JA, Peterson LB, Savage PB, Wills-Karp M, Ridgway WM, Wicker LS, Mattner J.

J Immunol. 2011 Jul 1;187(1):337-49. doi: 10.4049/jimmunol.1003525. Epub 2011 May 25.


Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice.

Rainbow DB, Moule C, Fraser HI, Clark J, Howlett SK, Burren O, Christensen M, Moody V, Steward CA, Mohammed JP, Fusakio ME, Masteller EL, Finger EB, Houchins JP, Naf D, Koentgen F, Ridgway WM, Todd JA, Bluestone JA, Peterson LB, Mattner J, Wicker LS.

J Immunol. 2011 Jul 1;187(1):325-36. doi: 10.4049/jimmunol.1003523. Epub 2011 May 25.


The soluble CTLA-4 splice variant protects from type 1 diabetes and potentiates regulatory T-cell function.

Gerold KD, Zheng P, Rainbow DB, Zernecke A, Wicker LS, Kissler S.

Diabetes. 2011 Jul;60(7):1955-63. doi: 10.2337/db11-0130. Epub 2011 May 20.


B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis.

Moritoki Y, Tsuda M, Tsuneyama K, Zhang W, Yoshida K, Lian ZX, Yang GX, Ridgway WM, Wicker LS, Ansari AA, Gershwin ME.

Cell Immunol. 2011;268(1):16-23. doi: 10.1016/j.cellimm.2011.01.005. Epub 2011 Jan 28.


CD8 T cells mediate direct biliary ductule damage in nonobese diabetic autoimmune biliary disease.

Yang GX, Wu Y, Tsukamoto H, Leung PS, Lian ZX, Rainbow DB, Hunter KM, Morris GA, Lyons PA, Peterson LB, Wicker LS, Gershwin ME, Ridgway WM.

J Immunol. 2011 Jan 15;186(2):1259-67. doi: 10.4049/jimmunol.1001597. Epub 2010 Dec 17.


Nonobese diabetic congenic strain analysis of autoimmune diabetes reveals genetic complexity of the Idd18 locus and identifies Vav3 as a candidate gene.

Fraser HI, Dendrou CA, Healy B, Rainbow DB, Howlett S, Smink LJ, Gregory S, Steward CA, Todd JA, Peterson LB, Wicker LS.

J Immunol. 2010 May 1;184(9):5075-84. doi: 10.4049/jimmunol.0903734. Epub 2010 Apr 2.


Idd9.2 and Idd9.3 protective alleles function in CD4+ T-cells and nonlymphoid cells to prevent expansion of pathogenic islet-specific CD8+ T-cells.

Hamilton-Williams EE, Wong SB, Martinez X, Rainbow DB, Hunter KM, Wicker LS, Sherman LA.

Diabetes. 2010 Jun;59(6):1478-86. doi: 10.2337/db09-1801. Epub 2010 Mar 18.


Multiplexed immunophenotyping of human antigen-presenting cells in whole blood by polychromatic flow cytometry.

Fung E, Esposito L, Todd JA, Wicker LS.

Nat Protoc. 2010 Feb;5(2):357-70. doi: 10.1038/nprot.2009.246. Epub 2010 Feb 4.


Fluorescence intensity normalisation: correcting for time effects in large-scale flow cytometric analysis.

Dendrou CA, Fung E, Esposito L, Todd JA, Wicker LS, Plagnol V.

Adv Bioinformatics. 2009:476106. doi: 10.1155/2009/476106. Epub 2009 Nov 17.


Idd9.1 locus controls the suppressive activity of FoxP3+CD4+CD25+ regulatory T-cells.

Yamanouchi J, Puertas MC, Verdaguer J, Lyons PA, Rainbow DB, Chamberlain G, Hunter KM, Peterson LB, Wicker LS, Santamaria P.

Diabetes. 2010 Jan;59(1):272-81. doi: 10.2337/db09-0648. Epub 2009 Oct 15.


Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice.

Araki M, Chung D, Liu S, Rainbow DB, Chamberlain G, Garner V, Hunter KM, Vijayakrishnan L, Peterson LB, Oukka M, Sharpe AH, Sobel R, Kuchroo VK, Wicker LS.

J Immunol. 2009 Oct 15;183(8):5146-57. doi: 10.4049/jimmunol.0802610. Epub 2009 Sep 25.


Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource.

Dendrou CA, Plagnol V, Fung E, Yang JH, Downes K, Cooper JD, Nutland S, Coleman G, Himsworth M, Hardy M, Burren O, Healy B, Walker NM, Koch K, Ouwehand WH, Bradley JR, Wareham NJ, Todd JA, Wicker LS.

Nat Genet. 2009 Sep;41(9):1011-5. doi: 10.1038/ng.434. Epub 2009 Aug 23.


Expression of diabetes-associated genes by dendritic cells and CD4 T cells drives the loss of tolerance in nonobese diabetic mice.

Hamilton-Williams EE, Martinez X, Clark J, Howlett S, Hunter KM, Rainbow DB, Wen L, Shlomchik MJ, Katz JD, Beilhack GF, Wicker LS, Sherman LA.

J Immunol. 2009 Aug 1;183(3):1533-41. doi: 10.4049/jimmunol.0900428. Epub 2009 Jul 10.

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