Bio

Bio


My professional goal as pediatrician specializing in immunology has been to challenge the limits of "inexplicable" and "untreatable" diseases, and apply current scientific knowledge to understand the mechanisms of impaired cellular immune function underlying the clinical manifestations and to develop curative treatments.

Following the completion of my pediatrics residency, I received training in molecular and cellular immunology in France (UNICET, Lyon) and the United States (DNAX Research Institute of Molecular and Cellular Biology, Palo Alto) under scientist, who critically influenced my scientific development. There, I was first exposed to the importance of integrating in depth laboratory research with clinical observations to develop a translational research approach to science. I then worked for fifteen years at the San Raffaele Scientific Institute in the Telethon Institute for Gene Therapy (HSR-TIGET), where I focused on dissecting the genetic and immunological basis of primary immunodeficiencies with autoimmune manifestations that might be treated by gene therapy.

Academic Appointments


  • Associate Professor (Research), Pediatrics

Honors & Awards


  • Associate Professor in Pediatrics, Italian Ministry of University (01/2014)

Boards, Advisory Committees, Professional Organizations


  • Member, European Society of Immunodeficiency (ESID) (2014 - Present)
  • Member, Federal of Clinical Immunology Societies (FOCIS and CIS) (2014 - Present)
  • Member, Italian Society of Pediatric Oncology and Hematology (AIEOP) (2014 - Present)
  • Associate Editor, Frontiers in Primary Immunodeficiencies (2014 - Present)
  • Reviewer, J Medical Genetics (2014 - Present)
  • Reviewer, J Autoimmunity (2014 - Present)
  • Reviewer, J Endocrinology (2014 - Present)
  • Reviewer, European Journal of Immunology (2014 - Present)
  • Reviewer, Transplantation (2014 - Present)
  • Grants revisions, European Research Council (2014 - Present)
  • Grants revisions, INSERM (2014 - Present)
  • Grants revision, LSBR Foundation (2014 - Present)
  • Grants revision, Wellcome Trust (2014 - Present)
  • Grants revision, ANR-France (2014 - Present)
  • Teaching activities ad Hoc lessons, Vita-Salute University Medical School and Biotechnology, Milan (2014 - Present)
  • Teaching activities ad hoc lessons, Tor Vergata University, Rome (2014 - Present)
  • Teaching activities ad hoc lessons, Undergraduate Course at Stanford University, Stanford, Palo Alto, CA (2014 - Present)

Professional Education


  • Fellowship, University of Turin, Italy, General Pediatrics Immunology (1991)
  • MD, University of Turin, Italy, Medicine (1987)

Patents


  • Rosa Bacchetta. "United States Patent WO2007/131575 Tr1 dendritic cells, method to generate regulatory type 1 T (Tr1) cells and uses thereof", Rosa Bacchetta, Apr 1, 2007
  • Rosa Bacchetta. "United States Patent 6884410 Methods for modulating antigen-specific immune responses", Rosa Bacchetta, Apr 26, 2005
  • Rosa Bacchetta. "United States Patent 6277635 Use of Interleukin-10 produce a population of suppressor cells", Rosa Bacchetta, Aug 21, 2001

Research & Scholarship

Current Research and Scholarly Interests


In the coming years, I plan to further determine the genetic and immunological basis of diseases with autoimmunity or immune dysregulation in children. I believe that much can still be learned from the in depth mechanistic studies of pediatric autoimmune diseases. Genomic analysis of the patients' samples has become possible which may provide a rapid indication of altered target molecules. I plan to implement robust functional studies to define the consequences of these genetic abnormalities and bridge them to the patient's clinical phenotype.

Understanding functional consequences of gene mutations in single case/family first and then validating the molecular and cellular defects in other patients with similar phenotypes, will anticipate and complement cellular and gene therapy strategies.

Publications

All Publications


  • Congenital diarrhoeal disorders: advances in this evolving web of inherited enteropathies NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY Canani, R. B., Castaldo, G., Bacchetta, R., Martin, M. G., Goulet, O. 2015; 12 (5): 293-302

    Abstract

    Congenital diarrhoeal disorders (CDDs) represent an evolving web of rare chronic enteropathies, with a typical onset early in life. In many of these conditions, severe chronic diarrhoea represents the primary clinical manifestation, whereas in others diarrhoea is only a component of a more complex multi-organ or systemic disorder. Typically, within the first days of life, diarrhoea leads to a life-threatening condition highlighted by severe dehydration and serum electrolyte abnormalities. Thus, in the vast majority of cases appropriate therapy must be started immediately to prevent dehydration and long-term, sometimes severe, complications. The number of well-characterized disorders attributed to CDDs has gradually increased over the past several years, and many new genes have been identified and functionally related to CDDs, opening new diagnostic and therapeutic perspectives. Molecular analysis has changed the diagnostic scenario in CDDs, and led to a reduction in invasive and expensive procedures. Major advances have been made in terms of pathogenesis, enabling a better understanding not only of these rare conditions but also of more common diseases mechanisms.

    View details for DOI 10.1038/nrgastro.2015.44

    View details for Web of Science ID 000354070800007

    View details for PubMedID 25782092

  • Forkhead box P3: The Peacekeeper of the Immune System INTERNATIONAL REVIEWS OF IMMUNOLOGY Passerini, L., de Sio, F. R., Roncarolo, M. G., Bacchetta, R. 2014; 33 (2): 129-145

    Abstract

    Ten years ago Forkhead box P3 (FOXP3) was discovered as master gene driving CD4(+)CD25(+) T cell regulatory (Treg) function. Since then, several layers of complexity have emerged in the regulation of its expression and function, which is not only exerted in Treg cells. While the mechanisms leading to the highly selective expression of FOXP3 in thymus-derived Treg cells still remain to be elucidated, we review here the current knowledge on the role of FOXP3 in the development of Treg cells and the direct and indirect consequences of FOXP3 mutations on multiple arms of the immune response. Finally, we summarize the newly acquired knowledge on the epigenetic regulation of FOXP3, still largely undefined in human cells.

    View details for DOI 10.3109/08830185.2013.863303

    View details for Web of Science ID 000332870100005

    View details for PubMedID 24354325

  • Immunological Outcome in Haploidentical-HSC Transplanted Patients Treated with IL-10-Anergized Donor T Cells. Frontiers in immunology Bacchetta, R., Lucarelli, B., Sartirana, C., Gregori, S., Lupo Stanghellini, M. T., Miqueu, P., Tomiuk, S., Hernandez-Fuentes, M., Gianolini, M. E., Greco, R., Bernardi, M., Zappone, E., Rossini, S., Janssen, U., Ambrosi, A., Salomoni, M., Peccatori, J., Ciceri, F., Roncarolo, M. 2014; 5: 16-?

    Abstract

    T-cell therapy after hematopoietic stem cell transplantation (HSCT) has been used alone or in combination with immunosuppression to cure hematologic malignancies and to prevent disease recurrence. Here, we describe the outcome of patients with high-risk/advanced stage hematologic malignancies, who received T-cell depleted (TCD) haploidentical-HSCT (haplo-HSCT) combined with donor T lymphocytes pretreated with IL-10 (ALT-TEN trial). IL-10-anergized donor T cells (IL-10-DLI) contained T regulatory type 1 (Tr1) cells specific for the host alloantigens, limiting donor-vs.-host-reactivity, and memory T cells able to respond to pathogens. IL-10-DLI were infused in 12 patients with the goal of improving immune reconstitution after haplo-HSCT without increasing the risk of graft-versus-host-disease (GvHD). IL-10-DLI led to fast immune reconstitution in five patients. In four out of the five patients, total T-cell counts, TCR-Vβ repertoire and T-cell functions progressively normalized after IL-10-DLI. These four patients are alive, in complete disease remission and immunosuppression-free at 7.2 years (median follow-up) after haplo-HSCT. Transient GvHD was observed in the immune reconstituted (IR) patients, despite persistent host-specific hypo-responsiveness of donor T cells in vitro and enrichment of cells with Tr1-specific biomarkers in vivo. Gene-expression profiles of IR patients showed a common signature of tolerance. This study provides the first indication of the feasibility of Tr1 cell-based therapy and paves way for the use of these Tr1 cells as adjuvant treatment for malignancies and immune-mediated disorders.

    View details for DOI 10.3389/fimmu.2014.00016

    View details for PubMedID 24550909

  • Gene/Cell Therapy Approaches for Immune Dysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome CURRENT GENE THERAPY Passerini, L., de Sio, F. R., Porteus, M. H., Bacchetta, R. 2014; 14 (6): 422-428
  • CD4(+) T Cells from IPEX Patients Convert into Functional and Stable Regulatory T Cells by FOXP3 Gene Transfer SCIENCE TRANSLATIONAL MEDICINE Passerini, L., Mel, E. R., Sartirana, C., Fousteri, G., Bondanza, A., Naldini, L., Roncarolo, M. G., Bacchetta, R. 2013; 5 (215)

    Abstract

    In humans, mutations in the gene encoding for forkhead box P3 (FOXP3), a critically important transcription factor for CD4⁺CD25⁺ regulatory T (T(reg)) cell function, lead to a life-threatening systemic poly-autoimmune disease, known as immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Severe autoimmunity results from the inborn dysfunction and instability of FOXP3-mutated T(reg) cells. Hematopoietic stem cell transplantation is the only current curative option for affected patients. We show here that when CD4⁺ T cells are converted into T(reg) cells after lentivirus-mediated FOXP3 gene transfer, the resulting CD4(FOXP3) T cell population displays stable phenotype and suppressive function, especially when naïve T cells are converted. We further demonstrate that CD4(FOXP3) T cells are stable in inflammatory conditions not only in vitro but also in vivo in a model of xenogeneic graft-versus-host disease. We therefore applied this FOXP3 gene transfer strategy for the development of a T(reg) cell-based therapeutic approach to restore tolerance in IPEX syndrome. IPEX-derived CD4(FOXP3) T cells mirrored T(reg) cells from healthy donors in terms of cellular markers, anergic phenotype, cytokine production, and suppressive function. These findings pave the way for the treatment of IPEX patients by adoptive cell therapy with genetically engineered T(reg) cells and are seminal for future potential application in patients with autoimmune disorders of different origin.

    View details for DOI 10.1126/scitranslmed.3007320

    View details for Web of Science ID 000328685500005

    View details for PubMedID 24337481

  • Autoantibodies to Harmonin and Villin Are Diagnostic Markers in Children with IPEX Syndrome PLOS ONE Lampasona, V., Passerini, L., Barzaghi, F., Lombardoni, C., Bazzigaluppi, E., Brigatti, C., Bacchetta, R., Bosi, E. 2013; 8 (11)

    Abstract

    Autoantibodies to enterocyte antigens harmonin (75 kDa USH1C protein) and villin (actin-binding 95 kDa protein) are associated with the Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome. In this study we evaluated the diagnostic value of harmonin and villin autoantibodies in IPEX and IPEX-like syndromes. Harmonin and villin autoantibodies were measured by a novel Luminescent-Immuno-Precipitation-System (LIPS) quantitative assay, in patients with IPEX, IPEX-like syndrome, Primary Immunodeficiencies (PID) with enteropathy, all diagnosed by sequencing of the FOXP3 gene, and in type 1 diabetes (T1D), celiac disease and healthy blood donors as control groups. Harmonin and villin autoantibodies were detected in 12 (92%) and 6 (46%) of 13 IPEX patients, and in none of the IPEX-like, PID, T1D, celiac patients, respectively. All IPEX patients, including one case with late and atypical clinical presentation, had either harmonin and/or villin autoantibodies and tested positive for enterocyte antibodies by indirect immunofluorescence. When measured in IPEX patients in remission after immunosuppressive therapy or hematopoietic stem cell transplantation, harmonin and villin autoantibodies became undetectable or persisted at low titers in all cases but one in whom harmonin autoantibodies remained constantly high. In one patient, a peak of harmonin antibodies paralleled a relapse phase of enteropathy. Our study demonstrates that harmonin and villin autoantibodies, measured by LIPS, are sensitive and specific markers of IPEX, differentiate IPEX, including atypical cases, from other early childhood disorders associated with enteropathy, and are useful for screening and clinical monitoring of affected children.

    View details for DOI 10.1371/journal.pone.0078664

    View details for Web of Science ID 000327216200039

    View details for PubMedID 24250806

  • Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells NATURE MEDICINE Gagliani, N., Magnani, C. F., Huber, S., Gianolini, M. E., Pala, M., Licona-Limon, P., Guo, B., Herbert, D. R., Bulfone, A., Trentini, F., Di Serio, C., Bacchetta, R., Andreani, M., Brockmann, L., Gregori, S., Flavell, R. A., Roncarolo, M. 2013; 19 (6): 739-?

    Abstract

    CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases.

    View details for DOI 10.1038/nm.3179

    View details for Web of Science ID 000319981600023

    View details for PubMedID 23624599

  • Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity CLINICAL IMMUNOLOGY Goudy, K., Aydin, D., Barzaghi, F., Gambineri, E., Vignoli, M., Mannurita, S. C., Doglioni, C., Ponzoni, M., Cicalese, M. P., Assanelli, A., Tommasini, A., Brigida, I., Dellepiane, R. M., Martino, S., Olek, S., Aiuti, A., Ciceri, F., Roncarolo, M. G., Bacchetta, R. 2013; 146 (3): 248-261

    Abstract

    Cell-surface CD25 expression is critical for maintaining immune function and homeostasis. As in few reported cases, CD25 deficiency manifests with severe autoimmune enteritis and viral infections. To dissect the underlying immunological mechanisms driving these symptoms, we analyzed the regulatory and effector T cell functions in a CD25 deficient patient harboring a novel IL2RA mutation. Pronounced lymphoproliferation, mainly of the CD8(+) T cells, was detected together with an increase in T cell activation markers and elevated serum cytokines. However, Ag-specific responses were impaired in vivo and in vitro. Activated CD8(+)STAT5(+) T cells with lytic potential infiltrated the skin, even though FOXP3(+) Tregs were present and maintained a higher capacity to respond to IL-2 compared to other T-cell subsets. Thus, the complex pathogenesis of CD25 deficiency provides invaluable insight into the role of IL2/IL-2RA-dependent regulation in autoimmunity and inflammatory diseases.

    View details for DOI 10.1016/j.clim.2013.01.004

    View details for Web of Science ID 000316241700010

    View details for PubMedID 23416241

  • Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells BLOOD Kinnunen, T., Chamberlain, N., Morbach, H., Choi, J., Kim, S., Craft, J., Mayer, L., Cancrini, C., Passerini, L., Bacchetta, R., Ochs, H. D., Torgerson, T. R., Meffre, E. 2013; 121 (9): 1595-1603

    Abstract

    Regulatory T cells (Tregs) play an essential role in preventing autoimmunity. Mutations in the forkhead box protein 3 (FOXP3) gene, which encodes a transcription factor critical for Treg function, result in a severe autoimmune disorder and the production of various autoantibodies in mice and in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) patients. However, it is unknown whether Tregs normally suppress autoreactive B cells. To investigate a role for Tregs in maintaining human B-cell tolerance, we tested the reactivity of recombinant antibodies isolated from single B cells isolated from IPEX patients. Characteristics and reactivity of antibodies expressed by new emigrant/transitional B cells from IPEX patients were similar to those from healthy donors, demonstrating that defective Treg function does not impact central B-cell tolerance. In contrast, mature naive B cells from IPEX patients often expressed autoreactive antibodies, suggesting an important role for Tregs in maintaining peripheral B-cell tolerance. T cells displayed an activated phenotype in IPEX patients, including their Treg-like cells, and showed up-regulation of CD40L, PD-1, and inducibl T-cell costimulator (ICOS), which may favor the accumulation of autoreactive mature naive B cells in these patients. Hence, our data demonstrate an essential role for Tregs in the establishment and the maintenance of peripheral B-cell tolerance in humans.

    View details for DOI 10.1182/blood-2012-09-457465

    View details for Web of Science ID 000321750300021

    View details for PubMedID 23223361

  • Clinical Features and Follow-Up in Patients with 22q11.2 Deletion Syndrome JOURNAL OF PEDIATRICS Cancrini, C., Puliafito, P., Digilio, M. C., Soresina, A., Martino, S., Rondelli, R., Consolini, R., Ruga, E. M., Cardinale, F., Finocchi, A., Romiti, M. L., Martire, B., Bacchetta, R., Albano, V., Carotti, A., Specchia, F., Montin, D., Cirillo, E., Cocchi, G., Trizzino, A., Bossi, G., Milanesi, O., Azzari, C., Corsello, G., Pignata, C., Aiuti, A., Pietrogrande, M. C., Marino, B., Ugazio, A. G., Plebani, A., Rossi, P. 2014; 164 (6): 1475-?

    Abstract

    To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease.A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis.The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations (P = .015) and speech disorders (P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis.Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.

    View details for DOI 10.1016/j.jpeds.2014.01.056

    View details for Web of Science ID 000336503200046

    View details for PubMedID 24657119

  • Identification of STAT5A and STAT5B Target Genes in Human T Cells PLOS ONE Kanai, T., Seki, S., Jenks, J. A., Kohli, A., Kawli, T., Martin, D. P., Snyder, M., Bacchetta, R., Nadeau, K. C. 2014; 9 (1)
  • Identification of STAT5A and STAT5B target genes in human T cells. PloS one Kanai, T., Seki, S., Jenks, J. A., Kohli, A., Kawli, T., Martin, D. P., Snyder, M., Bacchetta, R., Nadeau, K. C. 2014; 9 (1)

    Abstract

    Signal transducer and activator of transcription (STAT) comprises a family of universal transcription factors that help cells sense and respond to environmental signals. STAT5 refers to two highly related proteins, STAT5A and STAT5B, with critical function: their complete deficiency is lethal in mice; in humans, STAT5B deficiency alone leads to endocrine and immunological problems, while STAT5A deficiency has not been reported. STAT5A and STAT5B show peptide sequence similarities greater than 90%, but subtle structural differences suggest possible non-redundant roles in gene regulation. However, these roles remain unclear in humans. We applied chromatin immunoprecipitation followed by DNA sequencing using human CD4(+) T cells to detect candidate genes regulated by STAT5A and/or STAT5B, and quantitative-PCR in STAT5A or STAT5B knock-down (KD) human CD4(+) T cells to validate the findings. Our data show STAT5A and STAT5B play redundant roles in cell proliferation and apoptosis via SGK1 interaction. Interestingly, we found a novel, unique role for STAT5A in binding to genes involved in neural development and function (NDRG1, DNAJC6, and SSH2), while STAT5B appears to play a distinct role in T cell development and function via DOCK8, SNX9, FOXP3 and IL2RA binding. Our results also suggest that one or more co-activators for STAT5A and/or STAT5B may play important roles in establishing different binding abilities and gene regulation behaviors. The new identification of these genes regulated by STAT5A and/or STAT5B has major implications for understanding the pathophysiology of cancer progression, neural disorders, and immune abnormalities.

    View details for DOI 10.1371/journal.pone.0086790

    View details for PubMedID 24497979

  • Tr1 cells and the counter-regulation of immunity: natural mechanisms and therapeutic applications. Current topics in microbiology and immunology Roncarolo, M. G., Gregori, S., Bacchetta, R., Battaglia, M. 2014; 380: 39-68

    Abstract

    T regulatory Type 1 (Tr1) cells are adaptive T regulatory cells characterized by the ability to secrete high levels of IL-10 and minimal amounts of IL-4 and IL-17. Recently, CD49b and LAG-3 have been identified as Tr1-cell-specific biomarkers in mice and humans. Tr1 cells suppress T-cell- and antigen-presenting cell- (APC) responses primarily via the secretion of IL-10 and TGF-β. In addition, Tr1 cells release granzyme B and perforin and kill myeloid cells. Tr1 cells inhibit T cell responses also via cell-contact dependent mechanisms mediated by CTLA-4 or PD-1, and by disrupting the metabolic state of T effector cells via the production of the ectoenzymes CD39 and CD73. Tr1 cells were first described in peripheral blood of patients who developed tolerance after HLA-mismatched fetal liver hematopoietic stem cell transplant. Since their discovery, Tr1 cells have been proven to be important in maintaining immunological homeostasis and preventing T-cell-mediated diseases. Furthermore, the possibility to generate and expand Tr1 cells in vitro has led to their utilization as cellular therapy in humans. In this chapter we summarize the unique and distinctive biological properties of Tr1 cells, the well-known and newly discovered Tr1-cell biomarkers, and the different methods to induce Tr1 cells in vitro and in vivo. We also address the role of Tr1 cells in infectious diseases, autoimmunity, and transplant rejection in different pre-clinical disease models and in patients. Finally, we highlight the pathological settings in which Tr1 cells can be beneficial to prevent or to cure the disease.

    View details for DOI 10.1007/978-3-662-43492-5_3

    View details for PubMedID 25004813

  • IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts BLOOD Berglund, L. J., Avery, D. T., Ma, C. S., Moens, L., Deenick, E. K., Bustamante, J., Boisson-Dupuis, S., Wong, M., Adelstein, S., Arkwright, P. D., Bacchetta, R., Bezrodnik, L., Dadi, H., Roifman, C. M., Fulcher, D. A., Ziegler, J. B., Smart, J. M., Kobayashi, M., Picard, C., Durandy, A., Cook, M. C., Casanova, J., Uzel, G., Tangye, S. G. 2013; 122 (24): 3940-3950

    Abstract

    B-cell responses are guided by the integration of signals through the B-cell receptor (BCR), CD40, and cytokine receptors. The common γ chain (γc)-binding cytokine interleukin (IL)-21 drives humoral immune responses via STAT3-dependent induction of transcription factors required for plasma cell generation. We investigated additional mechanisms by which IL-21/STAT3 signaling modulates human B-cell responses by studying patients with STAT3 mutations. IL-21 strongly induced CD25 (IL-2Rα) in normal, but not STAT3-deficient, CD40L-stimulated naïve B cells. Chromatin immunoprecipitation confirmed IL2RA as a direct target of STAT3. IL-21-induced CD25 expression was also impaired on B cells from patients with IL2RG or IL21R mutations, confirming a requirement for intact IL-21R signaling in this process. IL-2 increased plasmablast generation and immunoglobulin secretion from normal, but not CD25-deficient, naïve B cells stimulated with CD40L/IL-21. IL-2 and IL-21 were produced by T follicular helper cells, and neutralizing both cytokines abolished the B-cell helper capacity of these cells. Our results demonstrate that IL-21, via STAT3, sensitizes B cells to the stimulatory effects of IL-2. Thus, IL-2 may play an adjunctive role in IL-21-induced B-cell differentiation. Lack of this secondary effect of IL-21 may amplify the humoral immunodeficiency in patients with mutations in STAT3, IL2RG, or IL21R due to impaired responsiveness to IL-21.

    View details for DOI 10.1182/blood-2013-06-506865

    View details for Web of Science ID 000329737600018

    View details for PubMedID 24159173

  • Combined DOCK8 and CLEC7A mutations causing immunodeficiency in 3 brothers with diarrhea, eczema, and infections JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Dinwiddie, D. L., Kingsmore, S. F., Caracciolo, S., Rossi, G., Moratto, D., Mazza, C., Sabelli, C., Bacchetta, R., Passerini, L., Magri, C., Bell, C. J., Miller, N. A., Hateley, S. L., Saunders, C. J., Zhang, L., Schroth, G. P., Barlati, S., Badolato, R. 2013; 131 (2): 594-597

    View details for DOI 10.1016/j.jaci.2012.10.062

    View details for Web of Science ID 000314661500045

    View details for PubMedID 23374272

  • Immunodeficiency with autoimmunity: beyond the paradox. Frontiers in immunology Bacchetta, R., Notarangelo, L. D. 2013; 4: 77-?

    View details for DOI 10.3389/fimmu.2013.00077

    View details for PubMedID 23630524

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