rosabacchetta_small

Malattie genetiche autoimmuni

Progetto di Ricerca TIGET
Rosa Bacchetta, Supervisore esterno

bacchetta.rosa@hsr.it



I diversi progetti del gruppo mirano a comprendere la patogenesi di malattie genetiche caratterizzate da perdita di tolleranza immunitaria e a definire nuove terapie cellulari e di trasferimento genico per ristabilire la regolazione immunitaria. La nostra ricerca parte dal paziente per studiare la biologia della malattia e per la ricerca di nuovi biomarcatori, e sviluppiamo strategie per modulare i meccanismi cellulari difettosi e per fornire nuove terapie a beneficio dei pazienti. Progetti innovativi di ricerca comprendono in particolare lo studio del controllo epigenetico del differenziamento del sistema immunitario adattativo, studi di genomica, transcrittomica, proteomica e genetica funzionale.

Pubblicazioni selezionate

Goettel JA, Biswas S, Lexmond WS, Yeste A, Passerini L, Patel B, Yang S, Sun J, Ouahed J, Shouval DS, McCann KJ, Horwitz BH, Mathis D, Milford EL, NotarangeloLD, Roncarolo MG, Fiebiger E, Marasco WA, Bacchetta R, Quintana FJ, Pai SY, Muise AM, Snapper SB. Fatal autoimmunity in mice reconstituted with human hematopoieticstem cells encoding defective FOXP3. Blood. 2015 Apr 1. pii:blood-2014-12-618363. [Epub ahead of print] PubMed PMID: 25833964.

Bacchetta R, Lucarelli B, Sartirana C, Gregori S, Lupo Stanghellini MT, MiqueuP, Tomiuk S, Hernandez-Fuentes M, Gianolini ME, Greco R, Bernardi M, Zappone E, Rossini S, Janssen U, Ambrosi A, Salomoni M, Peccatori J, Ciceri F, Roncarolo MG. Immunological Outcome in Haploidentical-HSC Transplanted Patients Treated withIL-10-Anergized Donor T Cells. Front Immunol. 2014. 5:16. doi:10.3389/fimmu.2014.00016. eCollection 2014. PubMed PMID: 24550909; PubMed Central PMCID: PMC3907718.

Pellerin L, Jenks JA, Bégin P, Bacchetta R, Nadeau KC. Regulatory T cells and their roles in immune dysregulation and allergy. Immunol Res. 2014. 58(2-3):358-68. doi: 10.1007/s12026-014-8512-5. Review. PubMed PMID:24781194; PubMed Central PMCID: PMC4161462.

Roncarolo MG, Gregori S, Bacchetta R, Battaglia M. Tr1 cells and thecounter-regulation of immunity: natural mechanisms and therapeutic applications. Curr Top Microbiol Immunol. 2014. 380:39-68. doi: 10.1007/978-3-662-43492-5-3. Review. PubMed PMID: 25004813.

Piras IS, Angius A, Andreani M, Testi M, Lucarelli G, Floris M, Marktel S,Ciceri F, La Nasa G, Fleischhauer K, Roncarolo MG, Bulfone A, Gregori S, Bacchetta R. BAT2 and BAT3 polymorphisms as novel genetic risk factors forrejection after HLA-related SCT. Bone Marrow Transplant. 2014. 49(11):1400-4. doi: 10.1038/bmt.2014.177. Epub 2014 Aug 11. Erratum in: Bone Marrow Transplant. 2014 Nov. 49(11):1452. Nasa, G La [corrected to La Nasa, G]. PubMed PMID:25111513; PubMed Central PMCID: PMC4222814.

Passerini L, Sio FR, Porteus MH, Bacchetta R. Gene/cell therapy approaches forImmune Dysregulation Polyendocrinopathy Enteropathy X-linked syndrome. Curr Gene Ther. 2014. 14(6):422-8. PubMed PMID: 25274247.

Passerini L, Santoni de Sio FR, Roncarolo MG, Bacchetta R. Forkhead box P3:the peacekeeper of the immune system. Int Rev Immunol. 2014. 33(2):129-45.doi: 10.3109/08830185.2013.863303. Epub 2013 Dec 19. Review. PubMed PMID:24354325.

Jenks JA, Seki S, Kanai T, Huang J, Morgan AA, Scalco RC, Nath R, Bucayu R, Wit JM, Al-Herz W, Ramadan D, Jorge AA, Bacchetta R, Hwa V, Rosenfeld R, NadeauKC. Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells. Clin Immunol. 2013. 148(2):227-36. doi: 10.1016/j.clim.2013.04.014. Epub 2013 May5. PubMed PMID: 23773921; PubMed Central PMCID: PMC4169138.

Bacchetta R, Notarangelo LD. Immunodeficiency with autoimmunity: beyond theparadox. Front Immunol. 2013. 4:77. doi: 10.3389/fimmu.2013.00077.eCollection 2013. PubMed PMID: 23630524; PubMed Central PMCID: PMC3624085.

Gagliani N, Magnani CF, Huber S, Gianolini ME, Pala M, Licona-Limon P, Guo B, Herbert DR, Bulfone A, Trentini F, Di Serio C, Bacchetta R, Andreani M, BrockmannL, Gregori S, Flavell RA, Roncarolo MG. Coexpression of CD49b and LAG-3identifies human and mouse T regulatory type 1 cells. Nat Med. 2013. 19(6):739-46. doi: 10.1038/nm.3179. Epub 2013 Apr 28. Erratum in: Nat Med.2014 Oct. 20(10):1217. PubMed PMID: 23624599.

Goudy K, Aydin D, Barzaghi F, Gambineri E, Vignoli M, Ciullini Mannurita S, Doglioni C, Ponzoni M, Cicalese MP, Assanelli A, Tommasini A, Brigida I, Dellepiane RM, Martino S, Olek S, Aiuti A, Ciceri F, Roncarolo MG, Bacchetta R. Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity. Clin Immunol. 2013. 146(3):248-61. doi: 10.1016/j.clim.2013.01.004. Epub 2013 Jan 24.

Kinnunen T, Chamberlain N, Morbach H, Choi J, Kim S, Craft J, Mayer L, Cancrini C, Passerini L, Bacchetta R, Ochs HD, Torgerson TR, Meffre E. Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells. Blood. 2013. 121(9):1595-603. doi: 10.1182/blood-2012-09-457465. Epub 2012 Dec 5.

Lampasona V, Passerini L, Barzaghi F, Lombardoni C, Bazzigaluppi E, Brigatti C, Bacchetta R, Bosi E. Autoantibodies to harmonin and villin are diagnostic markers in children with IPEX syndrome. PLoS One. 2013. 8(11):e78664. doi: 10.1371/journal.pone.0078664.

Passerini L, Mel ER, Sartirana C, Fousteri G, Bondanza A, Naldini L, Roncarolo MG, Bacchetta R. CD4⁺ T cells from IPEX patients convert into functional and stable regulatory T cells by FOXP3 gene transfer. Sci Transl Med. 2013. 5(215):215ra174. doi: 10.1126/scitranslmed.3007320

McMurchy AN, Gillies J, Gizzi MC, Riba M, Garcia-Manteiga JM, Cittaro D, Lazarevic D, Di Nunzio S, Piras IS, Bulfone A, Roncarolo MG, Stupka E, Bacchetta R, Levings MK. A novel function for FOXP3 in humans: intrinsic regulation of conventional T cells. Blood. 2013. 121(8):1265-75.

Passerini L, Santoni de Sio FR, Roncarolo MG, Bacchetta R. Forkhead box P3: The Peacekeeper of the Immune System. Int Rev Immunol. 2013. [Epub ahead of print]

Aiuti A, Bacchetta R, Seger R, Villa A, Cavazzana-Calvo M. Gene therapy for primary immunodeficiencies: Part 2. Curr Opin Immunol. 2012. 24(5):585-91.

Barzaghi F, Passerini L, Gambineri E, Ciullini Mannurita S, Cornu T, Kang ES, Choe YH, Cancrini C, Corrente S, Ciccocioppo R, Cecconi M, Zuin G, Discepolo V, Sartirana C, Schmidtko J, Ikinciogullari A, Ambrosi A, Roncarolo MG, Olek S, Bacchetta R. Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome. J Autoimmun. 2012. 38(1):49-58.

Barzaghi F, Passerini L, Bacchetta R. Immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome: a paradigm of immunodeficiency with autoimmunity. Front Immunol. 2012. 3:211.

Passerini L, Olek S, Di Nunzio S, Barzaghi F, Hambleton S, Abinun M, Tommasini A, Vignola S, Cipolli M, Amendola M, Naldini L, Guidi L, Cecconi M, Roncarolo MG, Bacchetta R. Forkhead box protein 3 (FOXP3) mutations lead to increased TH17 cell numbers and regulatory T-cell instability. J Allergy Clin Immunol. 2011. 128(6):1376-1379.e1.

Magnani CF, Alberigo G, Bacchetta R, Serafini G, Andreani M, Roncarolo MG, Gregori S. Killing of myeloid APCs via HLA class I, CD2 and CD226 defines a novel mechanism of suppression by human Tr1 cells. Eur J Immunol. 2011. 41(6):1652-62.

Roncarolo MG, Gregori S, Lucarelli B, Ciceri F, Bacchetta R. Clinical tolerance in allogeneic hematopoietic stem cell transplantation. Immunol Rev. 2011. 241(1):145-63.

Passerini L, Di Nunzio S, Gregori S, Gambineri E, Cecconi M, Seidel MG, Cazzola G, Perroni L, Tommasini A, Vignola S, Guidi L, Roncarolo MG, Bacchetta R. Functional type 1 regulatory T cells develop regardless of FOXP3 mutations in patients with IPEX syndrome. Eur J Immunol. 2011. 41(4):1120-31.

McMurchy AN, Gillies J, Allan SE, Passerini L, Gambineri E, Roncarolo MG, Bacchetta R, Levings MK. Point mutants of forkhead box P3 that cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked have diverse abilities to reprogram T cells into regulatory T cells. J Allergy Clin Immunol. 2010.126(6):1242-51.

Gregori S, Roncarolo MG, Bacchetta R. Methods for in vitro generation of human type 1 regulatory T cells. Methods Mol Biol. 2011. 677:31-46.

Bacchetta R, Gregori S, Serafini G, Sartirana C, Schulz U, Zino E, Tomiuk S, Jansen U, Ponzoni M, Paties CT, Fleischhauer K, Roncarolo MG. Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy. Haematologica. 2010. 95(12):2134-43.

Di Nunzio S, Cecconi M, Passerini L, McMurchy AN, Baron U, Turbachova I, Vignola S, Valencic E, Tommasini A, Junker A, Cazzola G, Olek S, Levings MK, Perroni L, Roncarolo MG, Bacchetta R. Wild-type FOXP3 is selectively active in CD4+CD25(hi) regulatory T cells of healthy female carriers of different FOXP3 mutations. Blood. 2009. 114(19):4138-41.

Serafini G, Andreani M, Testi M, Battarra M, Bontadini A, Biral E, Fleischhauer K, Marktel S, Lucarelli G, Roncarolo MG, Bacchetta R. Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia. Haematologica. 2009. 94(10):1415-26.

Seidel MG, Fritsch G, Lion T, Jürgens B, Heitger A, Bacchetta R, Lawitschka A, Peters C, Gadner H, Matthes-Martin S. Selective engraftment of donor CD4+25high FOXP3-positive T cells in IPEX syndrome after nonmyeloablative hematopoietic stem cell transplantation. Blood. 2009. 113(22):5689-91.

Amendola M, Passerini L, Pucci F, Gentner B, Bacchetta R, Naldini L. Regulated and multiple miRNA and siRNA delivery into primary cells by a lentiviral platform. Mol Ther. 2009. 17(6):1039-52.

McMurchy AN, Di Nunzio S, Roncarolo MG, Bacchetta R, Levings MK. Molecular regulation of cellular immunity by FOXP3. Adv Exp Med Biol. 2009. 665:30-46. Review.

Gambineri E, Perroni L, Passerini L, Bianchi L, Doglioni C, Meschi F, Bonfanti R, Sznajer Y, Tommasini A, Lawitschka A, Junker A, Dunstheimer D, Heidemann PH, Cazzola G, Cipolli M, Friedrich W, Janic D, Azzi N, Richmond E, Vignola S, Barabino A, Chiumello G, Azzari C, Roncarolo MG, Bacchetta R. Clinical and molecular profile of a new series of patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: inconsistent correlation between forkhead box protein 3 expression and disease severity. J Allergy Clin Immunol. 2008. 122(6):1105-1112.e1.

Allan SE, Broady R, Gregori S, Himmel ME, Locke N, Roncarolo MG, Bacchetta R, Levings MK. CD4+ T-regulatory cells: toward therapy for human diseases. Immunol Rev. 2008. 223:391-421.

Passerini L, Allan SE, Battaglia M, Di Nunzio S, Alstad AN, Levings MK, Roncarolo MG, Bacchetta R. STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells. Int Immunol. 2008. 20(3):421-31.

Allan SE, Alstad AN, Merindol N, Crellin NK, Amendola M, Bacchetta R, Naldini L, Roncarolo MG, Soudeyns H, Levings MK. Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Mol Ther. 2008. 16(1):194-202.

Bacchetta R, Gambineri E, Roncarolo MG. Role of regulatory T cells and FOXP3 in human diseases. J Allergy Clin Immunol. 2007. 120(2):227-35; quiz 236-7. Review.

Roncarolo MG, Gregori S, Battaglia M, Bacchetta R, Fleischhauer K, Levings MK. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev. 2006. 212:28-50. Review.

Bacchetta R, Passerini L, Gambineri E, Dai M, Allan SE, Perroni L, Dagna-Bricarelli F, Sartirana C, Matthes-Martin S, Lawitschka A, Azzari C, Ziegler SF, Levings MK, Roncarolo MG. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest. 2006. 116(6):1713-22.

Allan SE, Passerini L, Bacchetta R, Crellin N, Dai M, Orban PC, Ziegler SF, Roncarolo MG, Levings MK. The role of two FOXP3 isoforms in the generation of human CD4+ T regulatory cells. J Clin Invest. 2005. 115: 3276-3284. Prepublished Online October 6TH, 2005.

Allan SE, Bacchetta R, Levings MK. Book Editors: Gorczynski, R. The role of FOXP3 in the development and function of human CD4+CD25+ T regulatory cells. Altered Immunoregulation and Human Disease. 2006.

Gregori S, Mangia P, Bacchetta R, Tresoldi E, Kolbinger F, Traversari, C, Carballido JM, de Vries JE, Aversa G, Korthaeuer U, Roncarolo MG. An anti-CD45RO/RB monoclonal antibody modulates T-cell responses via induction of apoptosis and generation of regulatory T cells. J Exp Med. 2005. 201:1293-1305.

Bacchetta R, Gregori S, Roncarolo MG. Cd4+ Regulatory T Cells: Mechanisms of Induction and Effector Function. Autoimmunity Review. 2005. 4: 491-496.

Levings MK, Bacchetta R, Schulz U, Roncarolo MG. The role of IL-10 and TGF-ß in the differentiation and effector function of T regulatory cells. Int Arch Allergy Immunol. 2002. 129, 263-276.

Bacchetta R, Sartirana C, Levings MK, Bordignon C, Narula S, Roncarolo MG. Growth and expansion of human T regulatory type 1 cells are independent from TCR activation but require exogenous cytokines. Eur J Immunol. 2002. 32: 2237-2245.

Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK. Type 1 T regulatory cells. Immunol Rev. 2001. 182: 68-79.

Bacchetta R, Parkman R, McMahon M, Weinberg K, Bigler M, de Vries JE, Roncarolo MG. Dysfunctional cytokine production by host-reactive T cell clones isolated from a chimeric SCID patient transplanted with haploidentical bone marrow. Blood. 1995. 85:1944-1953.

Bacchetta R, Bigler M, Touraine JL, Parkman R, Tovo PA, Abrams J, de Waal Malefyt R, de Vries JE, Roncarolo MG. High levels of IL-10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J Exp Med. 1994. 179: 493-502.

 

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