PhD(Padua), Dip Microbiology
Professor Franca Ronchese completed her studies at the University of Padova, Italy and spent four years as a postdoctoral researcher at the National Institutes of Health, USA. She then worked as an independent Scientific Member at the Basel Institute for Immunology, Switzerland, before being awarded a Malaghan Senior Research Fellowship to establish her research programme at the Malaghan Institute in 1994.
The goal of our group’s research is to gain a better understanding of the initiation of allergic, or “T helper 2” (Th2), immune responses. These immune responses are associated with a characteristic inflammation profile that includes cells such as eosinophils, basophils, and mast cells, antibodies such as IgE, and cytokines such as IL-4, IL-5 and IL-13. While the effector phase of the Th2 response is well characterised, its early phases are not nearly as well understood. A number of Th2-inducing factors have been discovered, but none of these appears to play an essential role across different allergens and immune responses, suggesting that key factors that drive the differentiation of Th2 cells may still be unidentified.
Our current studies focus on dendritic cells, a rare type of immune cells whose function is to initiate immune responses. Dendritic cells are found in most tissues in our bodies and especially in the skin, the intestinal tract, and the airway. We have perfected techniques to label allergens with fluorescent markers, monitor their uptake by dendritic cells in vivo, and follow their transport to lymph nodes where they initiate immune responses. By using these fluorescence-labelled antigens in combination with flow cytometry and transcriptomics we are able to characterise in detail how allergen uptake alters the properties of dendritic cells and endows them with the ability to initiate Th2 immune responses. Results from these studies show that allergens impact the immune system at several levels, acting on dendritic cells directly, and also indirectly via the induction of innate cytokines in the tissue environment. By carrying out functional experiments we can alter or block the signalling of these innate cytokines in dendritic cells, assess their contribution to dendritic cell development, their expression of key mediators, and their priming of Th2 immune responses and subsequent allergic inflammation.
To increase the specificity of our models, we are also comparing allergen-treated dendritic cells to dendritic cells that have been exposed to other micro-organisms, such as bacteria and fungi, that prime Th responses of different phenotypes eg Th1 or Th17. We plan to compare the transcriptomes of dendritic cells exposed to these various stimuli to those of dendritic cells exposed to allergens. We expect that these studies will enable us to define the dendritic cell “Th2 signature” with a high level of precision.
Gilfillan CB, Kuhn S, Baey C, Hyde EJ, Yang J, Ruedl C, Ronchese F. (2018) Clec9A+ Dendritic Cells Are Not Essential for Antitumor CD8+ T Cell Responses Induced by Poly I:C Immunotherapy. J Immunol.
Ochiai S, Jagot F, Kyle RL, Hyde E, White RF, Prout M, Schmidt AJ, Yamane H, Lamiable O, Le Gros G, Ronchese F. (2018) Thymic stromal lymphopoietin drives the development of IL-13+ Th2 cells. Proc Natl Acad Sci U S A. 2
Pellefigues C, Tang SC, Schmidt A, White RF, Lamiable O, Connor LM, Ruedl C, Dobrucki J, Le Gros G, Ronchese F. (2017) Toll-Like Receptor 4, but Not Neutrophil Extracellular Traps, Promote IFN Type I Expression to Enhance Th2 Responses to Nippostrongylus brasiliensis. Front Immunol.
Webb LM, Lundie RJ, Borger JG, Brown SL, Connor LM, Cartwright AN, Dougall AM, Wilbers RH, Cook PC, Jackson-Jones LH, Phythian-Adams AT, Johansson C, Davis DM, Dewals BG, Ronchese F, MacDonald AS. (2017) Type I interferon is required for T helper (Th) 2 induction by dendritic cells. EMBO J.
Connor LM, Lamiable O, Ronchese F. (2017) Fetal dendritic cells give mum a break. Immunol Cell Biol.
White R, Pellefigues C, Ronchese F, Lamiable O, Eccles D. (2017) Investigation of chimeric reads using the MinION. F1000Res.
Connor LM, Tang SC, Cognard E, Ochiai S, Hilligan KL, Old SI, Pellefigues C, White RF, Patel D, Smith AA, Eccles DA, Lamiable O, McConnell MJ, Ronchese F (2017) Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles. J Exp Med
Hilligan KL, Connor LM, Schmidt AJ, Ronchese F (2016) Activation-Induced TIM-4 Expression Identifies Differential Responsiveness of Intestinal CD103+ CD11b+ Dendritic Cells to a Mucosal Adjuvant. PLoS One
Steiger S, Kuhn S, Ronchese F, Harper J (2015) MSU crystals induce upregulation of NK1.1-dependent killing by macrophages and support tumor-resident NK1.1+ monocyte/macrophage populations in anti-tumor therapy.J Immunol
Kuhn S, Yang J, Hyde E, Harper J, Kirman J, Ronchese F (2015) L-1beta receptor-dependent priming of anti-tumor CD4 T cells and sustained anti-tumor immunity after peri-tumoral treatment with MSU and mycobacteria. OncoImmunology
Kuhn S, Yang J, Ronchese F (2015) Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy. Front Immunol
Daniels NJ, Hyde E, Ghosh S, Seo K, Price KM, Hoshino K, Kaisho T, Okada T, Ronchese F (2015) Antigen-specific cytotoxic T lymphocytes target airway CD103+ and CD11b+ dendritic cells to suppress allergic inflammation. Mucosal Immunol
Ochiai S, Roediger B, Abtin A, Shklovskaya E,Fazekas de St Groth B, Yamane H, Weninger‡ W, Le Gros G, Ronchese.F. (2014). CD326loCD103loCD11blo dermal dendritic cells are activated by Thymic Stromal Lymphopoietin during contact sensitization in mice. J Immunol.
Connor LM, Tang SC, Camberis M, Le Gros G, Ronchese F (2014) Helminth–conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo. J. Immunol.
Bouchery T, Kyle R, Ronchese F, Le Gos G. (2014) The differentiation of CD4+ T-helper cell subsets in the context of helminth parasite infection. Review article. Frontiers Immunol.
Anderson RJ, Tang C, Daniels NJ, Compton BJ, Hayman CM, Johnston KA, Knight DA, Gasser O, Poyntz HC, Ferguson PM, Larsen DS, Ronchese F, Painter GF, Hermans, IF. (2014) ‘A novel synthetic self-adjuvanting lipopeptide vaccine to induce cytotoxic T lymphocytes that suppress allergic disease’. Nature Chemical Biology.
Ochiai S, Roediger B, Abtin A, Shklovskaya E, Fazekas de St Groth B, Yamane H, Weninger W‡, Le Gros G, Ronchese F (2014) CD326loCD103loCD11blo dermal dendritic cells are activated by Thymic Stromal Lymphopoietin during contact sensitization in mice. J Immunol.
Connor LM, Tang SC, Camberis M, Le Gros G, Ronchese F (2014) Helminth–conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo. J. Immunol.
Weinkove R, Brooks C, Carter J, Hermans I, Ronchese F (2013) Efficient depletion of chronic lymphocytic leukemia B cells using serial rounds of immunomagnetic depletion.J Immunol Methods
Kuhn S, Ronchese F (2013) Monocyte-derived dendritic cells: Emerging players in the antitumor immune response.Oncoimmunology,
Kuhn S, Hyde EJ, Yang J, Rich FJ, Harper JL, Kirman JR, Ronchese F (2013) Increased numbers of monocyte-derived dendritic cells during successful tumor immunotherapy with immune-activating agents.J Immunol
Ataera H, Simkins HM, Hyde E, Yang J, Hermans IF, Petersen TR, Ronchese F (2013) The control of CD8+ T cell responses is preserved in perforin-deficient mice and released by depletion of CD4+ CD25+ regulatory T cells. J Leukoc Biol,
Weinkove R, Brooks CR, Carter JM, Hermans IF, Ronchese F (2013) Functional invariant natural killer T cell and CD1d axis in chronic lymphocytic leukemia: implications for immunotherapy.Haematologica
Weinkove R, Brooks C, Carter JM, Hermans IF, Ronchese F (2013) Efficient depletion of chronic lymphocytic leukemia B cells using serial rounds of immunomagnetic depletion.J Immunol Methods, (in press)
Kuhn S, Hyde EJ, Yang J, Rich FJ, Harper JL, Kirman JR, Ronchese F (2013) Increased numbers of monocyte-derived dendritic cells during successful tumor immunotherapy with immune-activating agents. J Immunol, (in press)
Ataera H, Simkins HM, Hyde E, Yang J, Hermans IF, Petersen TR, Ronchese F (2013) The control of CD8+ T cell responses is preserved in perforin-deficient mice and released by depletion of CD4+ CD25+ regulatory T cells.J Leukoc Biol
Rich FJ, Kuhn S, Hyde EJ, Harper JL, Ronchese F, Kirman JR (2012) Induction of T cell responses and recruitment of an inflammatory dendritic cell subset following tumour immunotherapy with Mycobacterium smegmatis.Cancer Immunol Immunother
Ma Z-I, Lim SN, Qin JS, Yang J, Enomoto N, Ruedl C, Ronchese F (2012) Murine CD4+ T cell responses are inhibited by cytotoxic T cell-mediated killing of dendritic cells and are restored by antigen transfer.PLoS One
Ma Z-I, Yang J, Qin JS, Richter A, Perret R, El-Deiry WS, Finnberg N, Ronchese F (2012) Inefficient boosting of antitumour CD8(+) T cells by dendritic-cell vaccines is rescued by restricting T-cell cytotoxic functions.Oncoimmunology
Lim SN, Kuhn S, Hyde E, Ronchese F (2012) Combined TLR stimulation with Pam3Cys and Poly I:C enhances Flt3-ligand dendritic cell activation for tumor immunotherapy.J Immunother
Enomoto N, Hyde E, Ma JZ, Yang J, Forbes-Blom E, Delahunt B, Le Gros G, Ronchese F (2012) Allergen-specific CTL require perforin expression to suppress allergic airway inflammation. J Immunol, 188:1734-41
Zhi-long Ma J, Yang J, Qin JS, Richter A, Perret R, El-Deiry WS, Finnberg N, Ronchese F (2012) Inefficient boosting of antitumour CD8(+) T cells by dendritic-cell vaccines is rescued by restricting T cell cytotoxic functions. Oncoimmunology, 1:1507-16
Ataera H, Hyde E, Price KM, Stoitzner P, Ronchese F (2011) Murine melanoma-infiltrating dendritic cells are defective in antigen-presenting function regardless of the presence of CD4CD25 regulatory T cells. PLoS One, 6:e17515
Simkins HM, Hyde E, Farrand KJ, Ong ML, Degli-Esposti MA, Hermans IF, Ronchese F (2011) Administration of alpha-galactosylceramide impairs the survival of dendritic cell subpopulations in vivo. J Leukoc Biol, 89:753-62
Petersen TR, Sika-Paotonu D, Knight DA, Dickgreber N, Farrand KJ, Ronchese F, Hermans IF (2010) Potent anti-tumour responses to immunization with dendritic cells loaded with tumor tissue and an NKT cell ligand. Immunol Cell Biol, 88:596-604
Robinson MJ, Ronchese F, Miller JH, La Flamme AC (2010) Paclitaxel inhibits killing by murine cytotoxic T lymphocytes in vivo but not in vitro. Immunol Cell Biol, 88:291-6
Dickgreber N, Stoitzner P, Bai Y, Price KM, Farrand KJ, Manning K, Angel CE, Dunbar PR, Ronchese F, Fraser JD, Bäckström BT, Hermans IF (2009) Targeting antigen to MHC class II molecules promotes efficient cross-presentation and enhances immunotherapy. J Immunol, 182:1260-9
Farrand KJ, Dickgreber N, Stoitzner P, Ronchese F, Petersen TR, Hermans IF (2009) Langerin+CD8alpha+ dendritic cells are critical for cross-priming and IL-12 production in response to systemic antigens. J Immunol, 183:7732-42
Tripp CH, Sparber F, Hermans IF, Romani N, Stoitzner P (2009) Glycolipids injected into the skin are presented to NKT cells in the draining lymph node independently of migratory skin dendritic cells. J Immunol, 182:7644-54
Andrew KA, Simkins HM, Witzel S, Perret R, Hudson J, Hermans IF, Ritchie DS, Yang J, Ronchese F (2008) Dendritic cells treated with lipopolysaccharide up-regulate serine protease inhibitor 6 and remain sensitive to killing by cytotoxic T lymphocytes in vivo. J Immunol, 181:8356-62
Huck SP, Tang S-C, Andrew KA, Yang J, Harper JL, Ronchese F (2008) Activation and route of administration both determine the ability of bone marrow-derived dendritic cells to accumulate in secondary lymphoid organs and prime CD8+ T cells against tumours. Cancer Immunol Immunother, 57:63-71
Peacey M, Wilson S, Perret R, Ronchese F, Ward VK, Young V, Young SL, Baird MA (2008) Virus-like particles from rabbit hemorrhagic disease virus can induce an anti-tumor response. Vaccine, 26:5334-7
Perret R, Ronchese F (2008) Effector CD8(+) T cells activated in vitro confer immediate and long-term tumor protection in vivo. Eur J Immunol, 38:2886-95
Perret R, Ronchese F (2008) Memory T cells in cancer immunotherapy: which CD8 T-cell population provides the best protection against tumours? Tissue Antigens, 72:187-94
Stoitzner P, Green LK, Jung JY, Price KM, Ataera H, Kivell B, Ronchese F (2008) Inefficient presentation of tumor-derived antigen by tumor-infiltrating dendritic cells. Cancer Immunol Immunother, 57:1665-73
Stoitzner P, Green LK, Jung JY, Price KM, Tripp CH, Malissen B, Kissenpfennig A, Hermans IF, Ronchese F (2008) Tumor immunotherapy by epicutaneous immunization requires Langerhans cells. J Immunol, 180:1991-8
Matthews KE, Karabeg A, Roberts JM, Saeland S, Dekan G, Epstein MM, Ronchese F (2007) Long-term deposition of inhaled antigen in lung resident CD11b-CD11c+ Cells. Am J Respir Cell Mol Biol, 36:435-41
Matthews KE, Qin JS, Yang J, Hermans IF, Palmowski MJ, Cerundolo V, Ronchese F (2007) Increasing the survival of dendritic cells in vivo does not replace the requirement for CD4+ T cell help during primary CD8+ T cell responses. J Immunol, 179:5738-47
Pedersen AE, Ronchese F (2007) CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion. J Immune Based Ther Vaccines 5:9
Watt V, Ronchese F, Ritchie DS (2007) Resting B lymphocytes suppress tumour immunity via an MHC class-II dependent mechanism. J Immunother, 30:323-32
Matthews KE, Hermans IF, Roberts JM, Ching LM and Ronchese F (2006) DMXAA treatment of a non-immunogenic tumour does not synergise with active or passive CD8+ T cell immunotherapy. Immunol Cell Biol, 84:383-9
Ohta A, Gorelik E, Prasad S, Ronchese F, Lukashev D, Wong M, Huang X, Caldwell S, Liu K, Smith P, Chen JF, Jackson E, Apasov S, Abrams S, Sitkovsky M (2006) A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci USA, 103:1132-37
Ritchie D, Hermans I, Yang J, Walton J, Matthews K, Carter J, Findlay M, Dady P, Rawson P, Ronchese F (2006) Autologous dendritic cells pulsed with eluted peptide as immunotherapy for advanced B-cell malignancies. Leuk Lymphoma. 47:675-82
Stoitzner P, Tripp CH, Eberhart A, Price KM, Jung JY, Bursch L, Ronchese F, Romani N (2006) Langerhans cells cross-present antigen derived from skin. Proc Natl Acad Sci USA. 103:7783-8
Yang J, Huck SP, McHugh RS, Hermans IF and Ronchese F (2006) Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo. Proc Natl Acad Sci USA, 103:147-52
Harris NL, Holloway J, Fitzharris P, McDonald M, Camberis M, Fazekas de St Groth B, Ronchese F, Le Gros G (2005) Tissue localization and frequency of antigen-specific effector CD4 T cells determines the development of allergic airway inflammation. Immunol Cell Biol. 83:490-7
Kemp R, Bäckström T, Ronchese F (2005) The phenotype of Type 1 and Type 2 CD8+ T cells activated in vitro is affected by culture conditions and correlates with effector activity. Immunology, 115(3):315-24
Prasad S, Farrand K, Matthews S, Chang J, McHugh R, Ronchese F (2005) Dendritic cells loaded with stressed tumor cells elicit long lasting protective tumor immunity in mice depleted of CD4+CD25+ regulatory T cells. J Immunol, 174:90-98
van Panhuys N, Perret R, Prout M, Ronchese F, Le Gros G (2005) Effector Lymphoid Tissue and its critical role for protective immunity. Trends in Immunol. 26(5):242-7
Facchinetti A, Gallo P, Perini P, Mezzalira S, Ronchese F, Biasi G (2004) The MBP-reactive repertoire is shaped by recognition of minor histocompatibility antigens. J. Neuroimmunol, 148:154-61
Hermans I, Silk J, Yang J, Gileadi U, Palmowski M, McCarthy C, Ronchese F, Cerundolo V (2004) The VITAL assay: A versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo. J Immunol Methods, 285:25-40
Ritchie DS, Yang J, Hermans IF, Ronchese F (2004) B-Lymphocytes activated by CD40 ligand induce an antigen-specific anti-tumor immune response by direct and indirect activation of CD8+ T-cells. Scand J Immunol, 60:543-51
Roberts JM, Yang J, Ronchese F (2004) IL-4 deficiency does not impair the ability of dendritic cells to initiate CD4+ and CD8+ T cell responses in vivo. Int. Immunol. 16:1451-58
Lumsden, JM, Prasad SJ, Peach RJ, Ronchese F (2003) The effects of B7-dependent costimulation on T cell division and survival in vivo and in vitro are dependent on Ag concentration. Eur J Immunol. 33:2074-2082
Harris N, Watt V, Ronchese F, Le Gros G (2002) Differential T cell function and fate in lymph node and non-lymphoid tissues. J Exp Med, 195:317-26
Ronchese F (2002) Interview about killing of dendritic cells. Modern Aspects of Immunobiology, 2:100
Ronchese F, Prasad S, Ritchie D (2002) Tumour antigens on tap. The Lancet, 360:268
Chtanova T, Kemp R, Sutherland A, Ronchese F, Mackay C (2001) Gene microarrays reveal extensive differential gene expression in both CD4+ and CD8+ type 1 and type 2 T cells. J Immunol, 167:3057-63
Kemp RA, Ronchese F (2001) Tumor-specific Tc1 but not Tc2 cells deliver protective anti-tumor immunity. J Immunol, 167:6497-6502
Harris N, Prout M, Peach R, Fazekas de St Groth B, Ronchese F (2001) CD80 costimulation is required for Th2 cell cytokine production but not for antigen-specific accumulation and migration into the lung. J Immunol, 166:4908-14
Ronchese F, Hermans I (2001) Killing of dendritic cells: a life cut short, or a purposeful death? J Exp Med, 194: F23-6
Hermans I, Ritchie D, Roberts J, Yang J, Ronchese F (2000) CD8+ T cell-dependent elimination of dendritic cells in vivo limits the induction of anti-tumor immunity. J Immunol, 164:3095-101
Lumsden J, Roberts J, Harris N, Peach R, Ronchese F (2000) Differential requirement for CD80 and CD80/CD86 dependent costimulation in the lung immune response to an influenza virus infection. J Immunol, 164:79-85
Rawson P, Hermans I, Huck S, Roberts J, Pircher H, Ronchese, F (2000) Immunotherapy with dendritic cells and tumor MHC Class I-derived peptides requires high density of antigen on tumor cells. Cancer Res, 60:4493-98
Ritchie D, Hermans I, Lumsden J, Scanga C, Roberts J, Yang J, Kemp R, Ronchese F, (2000) Dendritic cell elimination as an assay of cytotoxic T lymphocyte activity in vivo. J Immunol Meth, 246:109-17
Harris N, Peach R, Ronchese F (1999) CTLA4-Ig inhibits optimal T helper 2 cell development but not protective immunity or memory response to Nippostrongylus brasiliensis. Eur J Immunol, 29, 311-316
Harris N, Ronchese F (1999) The role of B7 co-stimulation in T cell immunity. Immunol Cell Biol, 77: 304-311
Hermans I, Ritchie D, Daish A, Yang J, Kehry M, Ronchese F (1999) Impaired ability of MHC class II-/- dendritic cells to provide tumor protection is rescued by CD40 ligation. J Immunol, 163:77-81
McCoy K, Hermans I, Fraser H, Le Gros G, Ronchese F (1999) Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can regulate dendritic cell-induced activation and cytotoxicity of CD8+ T cells independently of CD4+ T cell help. J Exp Med, 189:1157-62
Hermans I, Daish A, Yang J, Ritchie D, Ronchese F (1998) Antigen expressed on tumor cells fails to elicit an immune response, even in the presence of increased numbers of tumor-specific cytotoxic T lymphocyte precursors. Cancer Res, 58:3909-17
Hermans I, Moroni-Rawson P, Ronchese F, Ritchie D (1998) The emerging role of the dendritic cell in novel cancer therapies. New Zeal Med J 111:111-113
Le Gros G, Erb K, Harris N, Holloway J, McCoy K, Ronchese, F (1998) Immunoregulatory networks in asthma. Clinical & Exp Allergy vol 28, suppl 5, 92-96
Harris N, Campbell C, Le Gros G, Ronchese F (1997) Blockade of CD28/B7 co-stimulation by mCTLA4-H1 inhibits antigen-induced lung eosinophilia but not Th2 cell development or recruitment in the lung. Eur J Immunol, 27:155-161
Harris N, Peach R, Naemura J, Linsley P, Le Gros G, Ronchese F (1997) CD80 co-stimulation is essential for the induction of airway eosinophilia. J Exp Med, 185:177-82
Hermans I, Daish A, Moroni-Rawson P, Ronchese F (1997) Tumor-peptide pulsed dendritic cells isolated from spleen or cultured in vitro from bone marrow precursors can provide protection against tumor challenge. Cancer Immunol Immunother, 44:341-47
Ronchese, F (1997) New strategies for tumour immunotherapy. NZ Science Review, 54:53-57
Garrigan K, Moroni-Rawson P, McMurray C, Hermans I, Abernethy N, Watson J, Ronchese F (1996) Functional comparison of spleen dendritic cells and dendritic cells cultured in vitro from bone marrow precursors. Blood, 88:3508-12.