• Carolina Jancic, PhD. Independent investigator – CONICET
• Jeremías Galletti, PhD. Clinical associated investigator – CONICET
• Florencia Sabbione, PhD. Assistant investigator – CONICET. Dir: Analía Trevani, PhD.

• Irene Keitelman, MSc. Post Doctoral student – CONICET. Dir: Analía Trevani, PhD.
• Maiumi Shiromizu, MSc. Doctoral student – CONICET. Dir: Analía Trevani, PhD
• Alexia Vereertbrugghen, MSc. Doctoral student – ANCyPT.
• Solana Snitman. Aztiria scholarship.

Our research is focused on two thematic axes:

1. To identify factors able to induce neutrophil activation or death, and the study of mechanisms that control various responses mediated by these cells.
2. To study mechanisms that regulate the function of γδ T lymphocytes and how these cells interact with neutrophils.

To study the molecular mechanisms involved in the export of IL-1 beta from neutrophils.

Our objective is to elucidate the processes that lead to the release of IL-1 beta to identify potential pharmacological targets to modulate its secretion in inflammatory processes in which IL-1 beta secreted by neutrophils plays a relevant role.

To determine the role of neutrophils in infection induced by Respiratory Syncytial Virus.

In particular, we are interested in elucidating the impact of NETs on infection and the immune response to the virus.

To determine the impact of hyperthermia within the febrile range on the development of inflammatory processes, focusing on regulating the effector functions of neutrophils.

To study the immunomodulatory properties of neutrophils, analyzing the regulation of the functionality of γδ T cells.

This line of work aims to elucidate the mechanisms through which neutrophils regulate the functionality of γδ T cells activated by various stimuli. It is also our interest to evaluate the action of γδ T cells on neutrophils, analyzing the type of response that they initiate after stimulation by γδ T cells.

1. Modulation of γδ T-cell activation by neutrophil elastase. Towstyka NY, Shiromizu CM, Keitelman I, Sabbione F, Salamone GV, Geffner JR, Trevani AS, Jancic CC. Immunology. 2017 Sep 9. doi: 10.1111/imm.12835. [Epub ahead of print] PMID: 28888033
2. Neutrophil Extracellular Traps Stimulate Proinflammatory Responses in Human Airway Epithelial Cells. Sabbione F, Keitelman IA, Iula L, Ferrero M, Giordano MN, Baldi P, Rumbo M, Jancic C, Trevani AS. J Innate Immun. 2017;9(4):387-402. doi: 10.1159/000460293. Epub 2017 May 4. PMID: 28467984
3. Induction of Neutrophil Extracellular Traps in Shiga Toxin-Associated Hemolytic Uremic Syndrome. Ramos MV, Mejias MP, Sabbione F, Fernandez-Brando RJ, Santiago AP, Amaral MM, Exeni R, Trevani AS, Palermo MS. J Innate Immun. 2016;8(4):400-11. doi: 10.1159/000445770. Epub 2016 May 28. PMID: 27230920
4. Desiccating-stress-induced disruption of ocular surface immune tolerance drives dry eye disease. Guzmán M, Keitelman I, Sabbione F, Trevani AS, Giordano MN, Galletti JG. Clin Exp Immunol. 2015 Dec 21. doi: 10.1111/cei.12759.
5. Foot-and-mouth disease virus infection of dendritic cells triggers phosphorylation of ERK1/2 inducing class I presentation and apoptosis. Langellotti C, Cesar G, Soria I, Quattrocchi V, Jancic C, Zamorano P, Vermeulen M. Vaccine. 2015 Sep 11;33(38):4945-53. doi: 10.1016/j.vaccine.2015.07.038. Epub 2015 Jul 26.
6. Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN. Merlotti A, Dantas E, Remes Lenicov F, Ceballos A, Jancic C, Varese A, Rubione J, Stover S, Geffner J, Sabatté J. Hum Reprod. 2015 Jul;30(7):1545-56. doi: 10.1093/humrep/dev113. Epub 2015 May 23.
7. Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate. Gerber PP, Cabrini M, Jancic C, Paoletti L, Banchio C, von Bilderling C, Sigaut L, Pietrasanta LI, Duette G, Freed EO, Basile Gde S, Moita CF, Moita LF, Amigorena S, Benaroch P, Geffner J, Ostrowski M. J Cell Biol. 2015 May 11;209(3):435-52. doi: 10.1083/jcb.201409082. Epub 2015 May 4.
8. Restoring conjunctival tolerance by topical nuclear factor-κB inhibitors reduces preservative-facilitated allergic conjunctivitis in mice. Guzmán M, Sabbione F, Gabelloni ML, Vanzulli S, Trevani AS, Giordano MN, Galletti JG. Invest Ophthalmol Vis Sci. 2014 Sep 4;55(9):6116-26. doi: 10.1167/iovs.14-14075.
9. Neutrophils suppress γδ T-cell function. Sabbione F, Gabelloni ML, Ernst G, Gori MS, Salamone G, Oleastro M, Trevani A, Geffner J, Jancic CC. Eur J Immunol. 2014 Mar;44(3):819-30. doi: 10.1002/eji.201343664. Epub 2013 Dec 27.
10. NADPH oxidase derived reactive oxygen species are involved in human neutrophil IL-1β secretion but not in inflammasome activation. Gabelloni ML, Sabbione F, Jancic C, Fuxman Bass J, Keitelman I, Iula L, Oleastro M, Geffner JR, Trevani AS. Eur J Immunol. 2013 Dec;43(12):3324-35. doi: 10.1002/eji.201243089. Epub 2013 Sep 10.
11. Immature mouse granulocytic myeloid cells are characterized by production of ficolin-B.Weber-Steffens D, Hunold K, Kürschner J, Martinez SG, Elumalai P, Schmidt D, Trevani A, Runza VL, Männel DN. Mol Immunol. 2013 Dec;56(4):488-96. doi: 10.1016/j.molimm.2013.06.015. Epub 2013 Aug 1. Erratum in: Mol Immunol. 2015 Jan;99(1):604.
12. Mechanisms regulating neutrophil survival and cell death. Gabelloni ML, Trevani AS, Sabatté J, Geffner J. Semin Immunopathol. 2013 Jul;35(4):423-37. doi: 10.1007/s00281-013-0364-x. Epub 2013 Feb 1. Review.
13. Benzalkonium chloride breaks down conjunctival immunological tolerance in a murine model.Galletti JG, Gabelloni ML, Morande PE, Sabbione F, Vermeulen ME, Trevani AS, Giordano MN. Mucosal Immunol. 2013 Jan;6(1):24-34. doi: 10.1038/mi.2012.44. Epub 2012 Jun 13.
14. Uptake and intracellular trafficking of superantigens in dendritic cells. Ganem MB, De Marzi MC, Fernández-Lynch MJ, Jancic C, Vermeulen M, Geffner J, Mariuzza RA, Fernández MM, Malchiodi EL. PLoS One. 2013 Jun 14;8(6):e66244. doi: 10.1371/journal.pone.0066244. Print 2013.
15. Candida albicans delays HIV-1 replication in macrophages. Rodriguez Rodrigues C, Remes Lenicov F, Jancic C, Sabatté J, Cabrini M, Ceballos A, Merlotti A, Gonzalez H, Ostrowski M, Geffner J. PLoS One. 2013 Aug 23;8(8):e72814. doi: 10.1371/journal.pone.0072814. eCollection 2013.
16. Action of shiga toxin type-2 and subtilase cytotoxin on human microvascular endothelial cells. Amaral MM, Sacerdoti F, Jancic C, Repetto HA, Paton AW, Paton JC, Ibarra C. PLoS One. 2013 Jul 30;8(7):e70431. doi: 10.1371/journal.pone.0070431. Print 2013.
17. CXCL12 is a costimulator for CD4+ T cell activation and proliferation in chronic lymphocytic leukemia patients. Borge M, Nannini PR, Morande PE, Jancic C, Bistmans A, Bezares RF, Giordano M, Gamberale R. Cancer Immunol Immunother. 2013 Jan;62(1):113-24. doi: 10.1007/s00262-012-1320-7.
18. Low extracellular pH stimulates the production of IL-1β by human monocytes. Jancic CC, Cabrini M, Gabelloni ML, Rodríguez Rodrigues C, Salamone G, Trevani AS, Geffner J. Cytokine. 2012 Feb;57(2):258-68. doi: 10.1016/j.cyto.2011.11.013. Epub 2011 Dec 11.
19. Semen promotes the differentiation of tolerogenic dendritic cells.Remes Lenicov F, Rodriguez Rodrigues C, Sabatté J, Cabrini M, Jancic C, Ostrowski M, Merlotti A, Gonzalez H, Alonso A, Pasqualini RA, Davio C, Geffner J, Ceballos A. J Immunol. 2012 Nov 15;189(10):4777-86. doi: 10.4049/jimmunol.1202089. Epub 2012 Oct 12
20. The cytotoxic activity of Aplidin in chronic lymphocytic leukemia (CLL) is mediated by a direct effect on leukemic cells and an indirect effect on monocyte-derived cells. Morande PE, Zanetti SR, Borge M, Nannini P, Jancic C, Bezares RF, Bitsmans A, González M, Rodríguez AL, Galmarini CM, Gamberale R, Giordano M. Invest New Drugs. 2012 Oct;30(5):1830-40. doi: 10.1007/s10637-011-9740-3. Epub 2011 Sep 2
21. Epithelial cells activate plasmacytoid dendritic cells improving their anti-HIVactivity.Rodriguez Rodrigues C, Cabrini M, Remes Lenicov F, Sabatté J, Ceballos A, Jancic C, Raiden S, Ostrowski M, Silberstein C, Geffner J. PLoS One. 2011;6(12):e28709. doi: 10.1371/journal.pone.0028709. Epub 2011 Dec 7
22. Cholinergic modulation of dendritic cell function. Salamone G, Lombardi G, Gori S, Nahmod K, Jancic C, Amaral MM, Vermeulen M, Español A, Sales ME, Geffner J. J Neuroimmunol. 2011 Jul;236(1-2):47-56. doi: 10.1016/j.jneuroim.2011.05.007. Epub 2011 Jun 12.
23. Thioperamide induces CD4 CD25 Foxp3 regulatory T lymphocytes in the lungmucosa of allergic mice through its action on dendritic cells. Amaral MM, Alvarez CA, Langellotti C, Jancic C, Salamone G, Geffner J, Vermeulen M. J Asthma Allergy. 2011;4:93-102. doi: 10.2147/JAA.S23507. Epub 2011 Sep 26
24. cetylcholine polarizes dendritic cells toward a Th2-promoting profile.
    Gori S, Vermeulen M, Remes-Lenicov F, Jancic C, Scordo W, Ceballos A, Towstyka N, Bestach Y, Belli C, Sabbione F, Geffner J, Salamone G. Allergy. 2017 Feb;72(2):221-231. doi: 10.1111/all.12926. Epub 2016 Jun 30. PMID: 27138374
25. Trophoblast cells induce a tolerogenic profile in dendritic cells.
    Salamone G, Fraccaroli L, Gori S, Grasso E, Paparini D, Geffner J, Pérez Leirós C, Ramhorst R.Hum Reprod. 2012 Sep;27(9):2598-606. doi: 10.1093/humrep/des208. Epub 2012 Jun 20.
    PMID: 2271828
26. Neutrophils from chronic lymphocytic leukemia patients exhibit an increased capacity to release extracellular traps (NETs)
    Podaza E, Sabbione F, Risnik D, Borge M, Almejún MB, Colado A, Fernández-Grecco H, Cabrejo M, Bezares RF, Trevani A, Gamberale R, Giordano M. Cancer Immunol Immunother. 2017 Jan;66(1):77-89. doi: 10.1007/s00262-016-1921-7. Epub 2016 Oct 28. PMID: 27796477
27. Fever-range hyperthermia improves the anti-apoptotic effect induced by low pH on human neutrophils promoting a proangiogenic profile.
    Díaz FE, Dantas E, Cabrera M, Benítez CA, Delpino MV, Duette G, Rubione J, Sanjuan N, Trevani AS, Geffner J. Cell Death Dis. 2016 Oct 27;7(10):e2437. doi: 10.1038/cddis.2016.337. PMID: 27787523
28. Mucosal tolerance disruption favors disease progression in an extraorbital lacrimal gland excision model of murine dry eye. Guzmán M, Keitelman I, Sabbione F, Trevani AS, Giordano MN, Galletti JG. Exp Eye Res. 2016 Oct;151:19-22. doi: 10.1016/j.exer.2016.07.004. Epub 2016 Jul 18. Review. PMID: 27443502
29. Comparative Characterization of Shiga Toxin Type 2 and Subtilase Cytotoxin Effects on Human Renal Epithelial and Endothelial Cells Grown in Monolayer and Bilayer Conditions.Álvarez RS, Sacerdoti F, Jancic C, Paton AW, Paton JC, Ibarra C, Amaral MM.PLoS One. 2016 Jun 23;11(6):e0158180. doi: 10.1371/journal.pone.0158180. eCollection 2016. PMID: 27336788
30. A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses. Coria LM, Ibañez AE, Tkach M, Sabbione F, Bruno L, Carabajal MV, Berguer PM, Barrionuevo P, Schillaci R, Trevani AS, Giambartolomei GH, Pasquevich KA, Cassataro J. J Immunol. 2016 May 15;196(10):4014-29. doi: 0.4049/jimmunol.1501188. Epub 2016 Apr 15. PMID: 27084100
31. Staphylococcus aureus Induces Shedding of IL-1RII in Monocytes and Neutrophils. Giai C, Gonzalez CD, Sabbione F, Garofalo A, Ojeda D, Sordelli DO, Trevani AS, Gómez MI. J Innate Immun. 2016;8(3):284-98. doi: 10.1159/000443663. Epub 2016 Mar 12. PMID: 26967533
32. Desiccating stress-induced disruption of ocular surface immune tolerance drives dry eye disease. Guzmán M, Keitelman I, Sabbione F, Trevani AS, Giordano MN, Galletti JG. Clin Exp Immunol. 2016 May;184(2):248-56. doi: 10.1111/cei.12759. Epub 2016 Feb 15. PMID: 26690299