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Professor Franca Ronchese

Programme Leader - Ronchese Laboratory

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.

Franca heads the Ronchese laboratory investigating dendritic cell biology and their roles in the initiation of allergic and inflammatory responses.

"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 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."

PhD(Padua), Dip Microbiology

Publications

2024

Ronchese F, Webb GR, Ochiai S, Lamiable O, Brewerton M (2024). How type-2 dendritic cells induce Th2 differentiation: Instruction, repression, or fostering T cell-T cell communication? Allergy. 2024 Sep 26.

Lee JE, Kim M, Ochiai S, Kim SH, Yeo H, Bok J, Kim J, Park M, Kim D, Lamiable O, Lee M, Kim MJ, Kim HY, Ronchese F, Kwon SW, Lee H, Kim TG, Chung Y (2024). Tonic type 2 immunity is a critical tissue checkpoint controlling autoimmunity in the skin. Cell Rep. 43(7):114364

Hornsteiner F, Vierthaler J, Strandt H, Resag A, Fu Z, Ausserhofer M, Tripp CH, Dieckmann S, Kanduth M, Farrand K, Bregar S, Nemati N, Hermann-Kleiter N, Seretis A, Morla S, Mullins D, Finotello F, Trajanoski Z, Wollmann G, Ronchese F, Schmitz M, Hermans IF, Stoitzner P (2024). Tumor-targeted therapy with BRAF-inhibitor recruits activated dendritic cells to promote tumor immunity in melanoma. J Immunother Cancer. 12(4):e008606

2023

Schmidt AJ, Wright GD, Ronchese F, Price KM (2023). Skin Whole-Mount Immunofluorescent Staining Protocol, 3D Visualization, and Spatial Image Analysis. Curr Protoc. 3(6):e820

Ferrer-Font L, Schmidt A, Ronchese F, Price KM (2022). A guideline for the appropriate recognition of shared resource laboratories in publication. Cytometry A. 103(3):193-197

2022

Chandler J, Prout M, Old S, Morgan C, Ronchese F, Benoist C, Le Gros G (2022). BCL6 deletion in CD4 T cells does not affect Th2 effector mediated immunity in the skin. Immunol Cell Biol. 2022 Sep 30

Lamiable O, Brewerton M, Ronchese F (2022). IL-13 in dermal type-2 dendritic cell specialization: from function to therapeutic targeting. Eur J Immunol. 52(7):1047-1057

Lopez R, Li B, Keren-Shaul H, Boyeau P, Kedmi M, Pilzer D, Jelinski A, Yofe I, David E, Wagner A, Ergen C, Addadi Y, Golani O, Ronchese F, Jordan MI, Amit I, Yosef N (2022). DestVI identifies continuums of cell types in spatial transcriptomics data. Nat Biotechnol. 40(9):1360-1369

Jankovic D, Ciucci T, Coffman RL, Coquet JM, Le Gros G, Mosmann TR, Sher A, Ronchese F (2022). Comment on: Repositioning TH cell polarization from single cytokines to complex help. Nat Immunol. 2022 Feb 21

2021

Hilligan KL, Namasivayam S, Clancy CS, O'Mard D, Oland SD, Robertson SJ, Baker PJ, Castro E, Garza NL, Lafont BAP, Johnson R, Ronchese F, Mayer-Barber KD, Best SM, Sher A (2022). Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge. J Exp Med. 219(2):e20211862.

Mayer JU, Hilligan KL, Chandler JS, Eccles DA, Old SI, Domingues RG, Yang J, Webb GR, Munoz-Erazo L, Hyde EJ, Wakelin KA, Tang SC, Chappell SC, von Daake S, Brombacher F, Mackay CR, Sher A, Tussiwand R, Connor LM, Gallego-Ortega D, Jankovic D, Le Gros G, Hepworth MR, Lamiable O, Ronchese F (2021). Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization. Nat Immunol. 2021 Nov 18

2020

Hilligan KL, Tang SC, Hyde EJ, Roussel E, Mayer JU, Yang J, Wakelin KA, Schmidt AJ, Connor LM, Sher A, MacDonald AS, Ronchese F (2020). Dermal IRF4+ dendritic cells and monocytes license CD4+ T helper cells to distinct cytokine profiles. Nat Commun. 11(1):5637.

Hilligan KL, Ronchese F (2020). Antigen presentation by dendritic cells and their instruction of CD4+ T helper cell responses. Cell Mol Immunol. 17(6):587-599

Bosteels C, Neyt K, Vanheerswynghels M, van Helden MJ, Sichien D, Debeuf N, De Prijck S, Bosteels V, Vandamme N, Martens L, Saeys Y, Louagie E, Lesage M, Williams DL, Tang SC, Mayer JU, Ronchese F, Scott CL, Hammad H, Guilliams M, Lambrecht BN (2020). Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection. Immunity. S1074-7613(20)30163-1.

Ronchese F, Hilligan KL, Mayer JU (2020). Dendritic Cells and the Skin Environment. Curr Opin Immunol. 64:56-62.

Giladi A, Cohen M, Medaglia C, Baran Y, Li B, Zada M, Bost P, Blecher-Gonen R, Salame TM, Mayer JU, David E, Ronchese F, Tanay A, Amit I (2020). Dissecting cellular crosstalk by sequencing physically interacting cells. Nat Biotechnol. 38(5):629-637 

Shepherd AL, Smith AAT, Wakelin KA, Kuhn S, Yang J, Eccles DA, Ronchese F (2020). A semi-automated technique for adenoma quantification in the ApcMin mouse using FeatureCounter. Sci Rep. 10(1):3064 

Ferrer-Font L, Mehta P, Harmos P, Schmidt AJ, Chappell S, Price KM, Hermans IF, Ronchese F, le Gros G, Mayer JU (2020). High-dimensional analysis of intestinal immune cells during helminth infection. Elife. 9:e51678 

2019

Schmidt AJ, Mayer JU, Wallace PK, Ronchese F, Price KM (2019). Simultaneous Polychromatic Immunofluorescent Staining of Tissue Sections and Consecutive Imaging of up to Seven Parameters by Standard Confocal Microscopy. Curr Protoc Cytom. 91(1) 

Hyde EJ, Wakelin KA, Daniels NJ, Ghosh S, Ronchese F (2019) Similar immune mechanisms control experimental airway eosinophilia elicited by different allergens and treatment protocols. BMC Immunol 20(1):18

Blecher-Gonen R, Bost P, Hilligan KL, David E, Salame TM, Roussel E, Connor LM, Mayer JU, Bahar Halpern K, Tóth B, Itzkovitz S, Schwikowski B, Ronchese F, Amit I (2019) Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity. Cell Systems 8(2):109-121.e6

2018

Baey C, Yang J, Ronchese F, Harper JL (2018) HyperuricaemicUrahPlt2/Plt2mice show altered T cell proliferation and defective tumor immunity after local immunotherapy with Poly I:C. PLOS One 13(11):e0206827

Prout MS, Kyle RL, Ronchese F, Le Gros G (2018) IL-4 is a key requirement for IL-4 and IL-4/IL-13 expressing CD4 Th2 subsets in lung and skin. Front Immunol 9:1211

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

2017

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

2014

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.

2013

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

2012

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

2011

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

2010

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

2009

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

2008

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

2007

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

2006

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

2005

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

2004

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