Carlo Pucillo
e-mail: carlo.pucillo AT uniud.it
affiliation: Università di Udine
research area(s): Immunity And Infection, Cancer Biology
Course:
Biomedical and Biotechnological Sciences
University/Istitution: Università di Udine
University/Istitution: Università di Udine
Carlo Pucillo is associate professor in Immunology at School of Medicine of University of Udine. In his scientific career Prof. Carlo Pucillo has been involved in two main field as documented by his publications: i) molecular mechanism that regulate the B cell activation and differentiation; ii) the role of mast cell as “biosensor of microenvironment”. Moreover, Pucillo has been Visiting Scientist at NCI in Bethesda, MD-USA form 1991 to 1994 in the lab of R.J Hodes working on T cell activation and demonstrated that the co-stimulation B7/CD28 regulate the IL2 release from T cell and T cell activation. Moreover, from the 1985 to the 1990 prof Pucillo spent 3 months/year in the lab of H. Metzger and J. Rivera (pioneers of MC biology) studying on FcεRI and more recently, in collaboration with dr Rivera, Pucillo has published several paper on the MC activation and on the influence of microenvironment on MC as well the crosstalk and the reciprocal influence between MC and T eff and/or Treg and/or B cell and how these interaction influence the immune response in cancer, autoimmunity or infections.
The Pucillo’s lab is using an interdisciplinary approach that includes cellular and molecular biology, mouse genetics and immunological and biochemical methods to study the role of Mast cell as an antenna of microenvironment and subsequently in the regulation of the adaptive response of the tissue as well as release chemical mediator which act as modulator of immune response. This body of work may provide a conceptual framework to therapeutically manipulate these responses in the settings of autoimmune disease and cancer. In fact Mast cells, which are scattered in skin and mucosa, have been considered sentinels of innate immunity. They are the lead effector cells in the immediate responses that can occur when sensitized individuals contact allergen through outer body surfaces. On the other hand a more defensive role in early responses to bacterial or parasitic pathogens has become recognized in recent years. In both situations, mast cells also follow up by recruiting larger cohorts of neutrophils and lymphocytes. Recent studies have shown that mast cells are heterogeneous, can produce an array of both pro- and anti-inflammatory mediators, can act as antigen-presenting cells and express a spectrum of co-stimulatory molecules. By sensing the microenvironment, reacting to specific and nonspecific stimuli, and secreting a broad spectrum of preformed and newly synthesized factors, MCs may represent the most adaptable cell type that functions in orchestrating the first response to foreign Ags and in directing adaptive-immune responses. These findings indicate that mast cells are far more functionally diverse than previously imagined and can function as immunoregulatory cells that influence both innate and adaptive immunity. Recent studies suggest, however, that this picture may still be incomplete and illustrate how mast cells are important in the complex cellular chains that lead to the activation of the normal immune response or in pathological context to the autoimmune disease. Pucillo’s lab has demonstrated a new model of regulation of immune system in normal and pathological condition. Novel clinical and basic studies have strengthen the idea that the MC are fundamental cells in the regulation of the immune system and acting on its activation state it is possible regulate the immune response against self in autoimmune disease or induce tolerance vs transplanted organs.
Selected publication 2008-2011
- Sibilano R., Gri G, Frossi B, Tripodo C, Suzuki R, Rivera J, Pucillo C. Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation. 2011 J. Leuk Biol. (in press)
- Frossi B, D’Incà F., Crivellato E, Sibilano R, Gri G, Mongillo M, Pucillo C. Single cell dynamics of Mast cell-Treg cell interaction Eur. J. Immunol. 2011 (in press)
- Bossi F, Frossi B, Tedesco F, Pucillo C. Novel insights into the pathogenesis and therapy of chronic urticaria. Allergy 2011 (in press)
- Vitale G, Mion F, Pucillo C. Regulatory B cells: evidence, developmentalorigin and population diversity. Mol Immunol. 2010 Nov-Dec;48(1-3):1-8.
- Tripodo C, Gri G, Piccaluga PP, Frossi B, Guarnotta C, Piconese S, Franco G, Vetri V, Pucillo CE, Florena AM, Colombo MP, Pileri SA. Mast Cells and Th17 Cells Contribute to the Lymphoma-Associated Pro-Inflammatory Microenvironment of Angioimmunoblastic T-Cell Lymphoma. Am J Pathol. 2010 Aug;177(2):792-802
- Frossi B, Gri G, Tripodo C, Pucillo C. Exploring a regulatory role for mast cells: ‘MCregs’? Trends Immunol. 2010 Mar;31(3):97-102.
- Merluzzi S, Frossi B, Gri G, Parusso S, Tripodo C, Pucillo C. Mast cells enhance proliferation of B lymphocytes and drive their differentiation towards IgA-secreting plasma cells. Blood. 2010 Apr 8;115(14):2810-7
- Tripodo C, Iannitto E, Florena A.M., Pucillo C, Piccaluga PP, Franco V and Pileri SA. amma-delta T-cell Lymphomas Nat Rev Clin Oncol. 2009 Dec;6(12):707-17.
- Piconese S., Gri G, Tripodo C, Musio S, Gorzanelli A, Frossi B, Pedotti R, Pucillo C and Colombo M Mast cells counteract regulatory T cell suppression through interleukin-6 and OX40/OX40L axis toward Th17 cell differentiation. Blood. 2009 Sep 24;114(13):2639-48.
- Bossi F, Rizzi L, Bulla R, Debeus A, Tripodo C, Picotti P, Betto E, Macor P, Pucillo C, Würzner R, Tedesco F. C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function. Blood. 2009 Apr 9;113(15):3640-8.
- Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, Tripodo C, Viola A, Odom S, Rivera J, Colombo MP, Pucillo CE. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity. 2008 Nov;29(5):771-81.
- Merluzzi S, Gri G, Gattei V, Pagano M, Pucillo C. APE/Ref-1 makes fine-tuning of CD40-induced B cell proliferation. Mol Immunol. 2008 Aug;45(14):3731-9.
- Frossi B., de Carli M., Piemonte M., Pucillo C. (2008) Oxidative stress exerts an opposite regulatory effect on cytokine production by Th1 and Th2 human T cells, 2008. Mol. Immunl 45(1):58-64.
- Merluzzi S., D'Orlando O., Leonardi A., Vitale G. and Carlo Pucillo TRAF2 and p38 are involved in B cells CD40-mediated APE/Ref-1 nuclear translocation: a novel pathway in B cell activation 2008. Mol. Immunol; 45(1):76-86.
- Sibilano R., Gri G, Frossi B, Tripodo C, Suzuki R, Rivera J, Pucillo C. Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation. 2011 J. Leuk Biol. (in press)
- Frossi B, D’Incà F., Crivellato E, Sibilano R, Gri G, Mongillo M, Pucillo C. Single cell dynamics of Mast cell-Treg cell interaction Eur. J. Immunol. 2011 (in press)
- Bossi F, Frossi B, Tedesco F, Pucillo C. Novel insights into the pathogenesis and therapy of chronic urticaria. Allergy 2011 (in press)
- Vitale G, Mion F, Pucillo C. Regulatory B cells: evidence, developmentalorigin and population diversity. Mol Immunol. 2010 Nov-Dec;48(1-3):1-8.
- Tripodo C, Gri G, Piccaluga PP, Frossi B, Guarnotta C, Piconese S, Franco G, Vetri V, Pucillo CE, Florena AM, Colombo MP, Pileri SA. Mast Cells and Th17 Cells Contribute to the Lymphoma-Associated Pro-Inflammatory Microenvironment of Angioimmunoblastic T-Cell Lymphoma. Am J Pathol. 2010 Aug;177(2):792-802
- Frossi B, Gri G, Tripodo C, Pucillo C. Exploring a regulatory role for mast cells: ‘MCregs’? Trends Immunol. 2010 Mar;31(3):97-102.
- Merluzzi S, Frossi B, Gri G, Parusso S, Tripodo C, Pucillo C. Mast cells enhance proliferation of B lymphocytes and drive their differentiation towards IgA-secreting plasma cells. Blood. 2010 Apr 8;115(14):2810-7
- Tripodo C, Iannitto E, Florena A.M., Pucillo C, Piccaluga PP, Franco V and Pileri SA. amma-delta T-cell Lymphomas Nat Rev Clin Oncol. 2009 Dec;6(12):707-17.
- Piconese S., Gri G, Tripodo C, Musio S, Gorzanelli A, Frossi B, Pedotti R, Pucillo C and Colombo M Mast cells counteract regulatory T cell suppression through interleukin-6 and OX40/OX40L axis toward Th17 cell differentiation. Blood. 2009 Sep 24;114(13):2639-48.
- Bossi F, Rizzi L, Bulla R, Debeus A, Tripodo C, Picotti P, Betto E, Macor P, Pucillo C, Würzner R, Tedesco F. C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function. Blood. 2009 Apr 9;113(15):3640-8.
- Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, Tripodo C, Viola A, Odom S, Rivera J, Colombo MP, Pucillo CE. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity. 2008 Nov;29(5):771-81.
- Merluzzi S, Gri G, Gattei V, Pagano M, Pucillo C. APE/Ref-1 makes fine-tuning of CD40-induced B cell proliferation. Mol Immunol. 2008 Aug;45(14):3731-9.
- Frossi B., de Carli M., Piemonte M., Pucillo C. (2008) Oxidative stress exerts an opposite regulatory effect on cytokine production by Th1 and Th2 human T cells, 2008. Mol. Immunl 45(1):58-64.
- Merluzzi S., D'Orlando O., Leonardi A., Vitale G. and Carlo Pucillo TRAF2 and p38 are involved in B cells CD40-mediated APE/Ref-1 nuclear translocation: a novel pathway in B cell activation 2008. Mol. Immunol; 45(1):76-86.
Project Title:
MULTIFACETED ROLES FOR MAST CELLS IN ADENOMA INITIATION, GROWTH AND PROGRESSION TO COLON CARCINOMA.
Gut, which is highly exposed to the external environment, and it is the site where the immune system, more than in any other part of the body, must face daily with toxins and pathogens and avoid inappropriate immune response to self. In this contest any changes in the gut can influence the immune system but on the other hand the tissue can be manipulated by the products of immune cells. This intimate link is not only present in physiological interactions, such as the maintenance of tissue homeostasis and repair, but even in pathological conditions, 'smoldering' inflammation in the tumor microenvironment has many tumor-promoting effects. In fact, inflammatory bowel disease (IBD), a condition of chronic inflammation of intestines, is associated with an increased risk of colorectal cancer that affects Western countries. However, the relationship between immune cells
and a nascent colorectal cancer are complex with some cells exerting protective effects, and others playing a tumor promoting role, along with cells that have both functions depending on the disease stage or the cell composition of the microenvironment. Mast cells (MCs), well-positioned to be one of the first cells of immune system to interact with environmental antigens, may play a role in carcinogenetic process in the gut since they are typically located underneath the intestinal epithelium and their activation may affect the mucosal barrier functions. Even though much evidence indicates MCs involvement in inflammatory and carcinogenetic processes in the colon, no conclusive data exist about their actual role in promoting or suppressing inflammation and cancer at this site. This project stems from the idea that MCs mediate the interplay between external injury and the immune system. It aims at the identification of the role of MCs in inflammatory-related colon carcinogenesis by applying a chemically-induced transformation model of this disease to MC deficient mice, thus allowing the characterization of cellular and molecular mechanisms underlying the complex interactions between MCs and regulatory partner players, and to analyze the contribution of MCs to the immunesuppressed environment of tumor tissue. Every single project section will contain an analysis of human counterpart of the pathological conditions under examination (inflammatory lesion, adenoma transformation, adeno-carcinoma, metastases), thus directly confirming in clinical settings the findings obtained in mouse samples. The results of this project will uncover new aspects of chronic inflammation-related cancer onset, will clarify MC contribution at different stages of the disease and will open new therapeutic strategies aiming at modulating MC regulatory functions
and a nascent colorectal cancer are complex with some cells exerting protective effects, and others playing a tumor promoting role, along with cells that have both functions depending on the disease stage or the cell composition of the microenvironment. Mast cells (MCs), well-positioned to be one of the first cells of immune system to interact with environmental antigens, may play a role in carcinogenetic process in the gut since they are typically located underneath the intestinal epithelium and their activation may affect the mucosal barrier functions. Even though much evidence indicates MCs involvement in inflammatory and carcinogenetic processes in the colon, no conclusive data exist about their actual role in promoting or suppressing inflammation and cancer at this site. This project stems from the idea that MCs mediate the interplay between external injury and the immune system. It aims at the identification of the role of MCs in inflammatory-related colon carcinogenesis by applying a chemically-induced transformation model of this disease to MC deficient mice, thus allowing the characterization of cellular and molecular mechanisms underlying the complex interactions between MCs and regulatory partner players, and to analyze the contribution of MCs to the immunesuppressed environment of tumor tissue. Every single project section will contain an analysis of human counterpart of the pathological conditions under examination (inflammatory lesion, adenoma transformation, adeno-carcinoma, metastases), thus directly confirming in clinical settings the findings obtained in mouse samples. The results of this project will uncover new aspects of chronic inflammation-related cancer onset, will clarify MC contribution at different stages of the disease and will open new therapeutic strategies aiming at modulating MC regulatory functions