This volume focuses on a challenging field in biomedicine: the genetic control of central immune tolerance. The thymus gland is a lymphoid organ implicated in T cells' maturation, differentiation, and selection. Its function is associated with the control of immune homeostasis in the body, establishing central immune tolerance, and preventing the onset of autoimmune diseases.

This book focuses on thymus development, their cellular components and their respective function, and the peculiar gene expression profiling (transcriptome) found in the medullary thymic epithelial cells (mTECs) that are implicated in the self-representation in the thymus and the Autoimmune regulator (Aire) gene. Chapters also explore the mutations in the Aire gene, manifestation of autoimmune diseases, and the role of cell-cell interactions within the thymus with implications in the negative selection (elimination) of nascent autoreactive T cells in preventing aggressive autoimmunity. This new edition includes two new chapters devoted to the genome editing of the Aire gene through Crispr-Cas9 system, and thymic involution.All chapters have been updated to reflect the latest research in the field.

Focuses on the cellular and molecular genetic control of central immune tolerance, a challenging field in biomedicine Brings together current knowledge on transcriptome and cell biology Offers a functional genomics perspective on the thymus

Autorentext

Geraldo Aleixo Passos received his PhD degree in biochemistry (1988) from Ribeirão Preto Medical School, University of São Paulo, USP, Brazil. His postdoctoral studies were conducted at the Molecular Genetics Institute of Montpellier (CNRS), France (1992-94), with sequencing and physical mapping of the human immunoglobulin lambda locus on chromosome 22q11.2. During several years, he worked in close collaboration in the former microarray laboratory at Centre d´Immunologie de Marseille-Luminy (CIML, Marseille, France) (1999-2001) and then in the Unité INSERM 1090 in Marseille (2002-17) to study the large-scale gene expression in the thymus. He is currently an Associate Professor (Genetics and Molecular Biology) at Ribeirão Preto School of Dentistry and at Ribeirão Preto Medical School (University of São Paulo, Campus of Ribeirão Preto, Brazil). He is head of the Molecular Immunogenetics Group at the Ribeirão Preto Medical School. He was the adviser of two PhD theses awarded by the Ministry of Education/CAPES: in 2008, one of his students received the CAPES Thesis Award, and in 2010, another student received the distinction CAPES Thesis Honor in Genetics.

Daniella Arêas Mendes-da-Cruz received her PhD degree in Parasitary Biology (2003) from the Oswaldo Cruz Foundation, followed by postdoctoral studies in T-lymphocyte migration in T-cell acute lymphoblastic leukemia and lymphoma (2004-2008) at the CNRS UMR 8147 - Hôpital Necker (Paris, France). Recently, she has worked as a visiting researcher at the University of Central Lancashire (2020-2022) and Lancaster University (2022-2023), United Kingdom. Her research focuses on studying the migration and differentiation of developing T-cells, emphasizing molecules involved in intrathymic processes. She is interested in understanding the neuroendocrine control of the immune system through the use of different models of autoimmune diseases (type 1 diabetes), infectious diseases (Zika-virus infection), neoplasias (T-cell acute lymphoblastic Leukemia and Lymphoma), and neurodevelopmental diseases (Autism Spectrum Disorder), with emphasis on the study of molecules involved in the processes of migration, survival, and activation of T-cells.

Wilson Savino graduated in Biological Sciences from the State University of Rio de Janeiro (1974), obtained his master's degree in Histology and Embryology from the Federal University of Rio de Janeiro (1979), PhD in Cellular and Tissue Biology from the University of São Paulo (1982), and developed a postdoctoral training in Cellular Immunology at the Necker Hospital, Paris (1983-1985). He is a Senior Researcher at the Oswaldo Cruz Foundation. He was President of the Brazilian Society of Immunology (1993-1995), the Brazilian Society of Cell Biology (2010-2014) and the International Society of Neuroimmunomodulation (2011-2014). He is a full member of the Brazilian Academy of Sciences, the World Academy of Sciences, and the World Academy of Sciences (TWAS). Furthermore, he is a member of the International Scientific Council of the Institut Pasteur Montevideo. He was Director of the Oswaldo Cruz Institute from 2013 to May 2017.

Inhalt

Chapter 1 - History of the Thymus.- Chapter 2 -Thymus Ontogeny and Development.- Chapter 3 -The ins and outs of thymic epithelial.- Chapter 4 - From T-Lineage Specification to Intrathymic Maturation.- Chapter 5 - Intrathymic cell migration.- Chapter 6 -Thymic crosstalk.- Chapter 7 - The Autoimmune Regulator (AIRE) Gene.- Chapter 8 - Aire mutations and Autoimmune Diseases.- Chapter 9 -The thymus as a mirror.- Chapter 10 -The CRISPR-Cas9 system.- Chapter 11 -Age-related thymic involution.- Chapter 12 - T-cell Recovery After Autologous.