Seminars in Cell & Developmental Biology 41 (2015) 1–2
Contents lists available at ScienceDirect
Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb
Editorial
In 1973, Ralph Steinman and Zanvil Cohn looked through a phase contrast microscope and discovered a cell type that was elongated and exhibited tree-like processes that were continually developing and contracting (Steinman and Cohn, 1973). This special accessory cell, named dendritic cell (DC) from the Greek word dendreon, set Steinman on a pathway spanning several decades to uncover that these cells were critical for processing and presenting antigens – a proposal met with considerable skepticism initially. In 2011, the intuitive insights of Steinman and Cohn and their research teams was awarded the Nobel Prize for Physiology or Medicine recognizing the transformative impact of their discovery in immunology and medicine. DC were shown to be responsible to prime the adaptive immune system, to influence the innate immune response and to have the ability to induce self-tolerance. To exert all these different functions, several specialized DC subsets have been found to exist and these often have tissue-specific localizations. This special review edition is composed of seven reviews which address several key aspects of DC biology including the definition of DC as a lineage, mouse and human DC development and the role of DC in tolerance induction and autoimmunity: In the first review, “Towards defining a lineage – The case for dendritic cells” by Leila Perie and Shalin Naik, the origin of DC subsets is discussed. All DC subsets arise from hematopoietic stem cells. Mature hematopoietic lineages are subdivided in lymphoid and myeloid-erythroid lineage. Lymphoid cells develop from a common lymphoid progenitor that has lost myeloid-erythroid lineage potential and comprises of T, B and innate lymphoid cells. Myeloiderythroid cell types derive from a common myeloid progenitor that has lost all lymphoid potential. Interestingly, DC are unique within the hematopoietic system in that they can arise from the lymphoid as well as the myeloid arm, indicating that DC subtypes could be considered as different lineages if the origin of a cell is used for the definition of a lineage. This review summarizes the recent data on DC development through the use of several lineage tracing techniques and propose an “overlap” model of lineage commitment. In “Dendritic cells and monocyte derived cells: two complementary and integrated functional systems”, Andreas Schlitzer, Naomi McGovern and Florent Ginhoux discuss the differences and similarities between DC and monocyte-derived cells (MC). The majority of DC, named conventional DC (cDC), derive from a common precursor and do not arise from monocytes. However, “inflammatory” DC are not present in the steady state but differentiate from monocytes during infection/inflammation. This review summarizes the latest findings of the organization of DC and MCs networks.
http://dx.doi.org/10.1016/j.semcdb.2015.05.010 1084-9521/© 2015 Published by Elsevier Ltd.
Two reviews focus on the skin and resident DC subtype, the Langerhans cells (LCs). LCs are a highly specialized DC subset and differ in their origin and molecular make up from the other DC subtypes. In “Establishing and maintaining the Langerhans cell network” Michael Chopin and Stephen Nutt describe the extrinsic and intrinsic mechanisms that govern LC lineage fate and function. The different developmental origins of LCs are discussed as well as the transcriptional network that governs LC identity. Thomas Hieronymus, Martin Zenke, Jea-Hyun-Baek and Kristin Sere address in “The clash of Langerhans cell homeostasis in skin: should I stay or should I go” the importance of certain receptor kinases in LC development and the role of epithelial-to-mesenchymal-transition and mesenchymal-to-epithelial-transition in the LC life cycle. In “BDCA3+ CLEC9A+ human dendritic cell function and development” by Evelyn van der Aa, Nadine van Montfort and Andrea Woltman, the authors give a comprehensive review of the newly identified human BDCA3+ CLEC9A+ human DC subset which are thought to be the human counterpart to mouse CD8␣+ and CD103+ DC. A detailed phenotypic description of BDCA3+ CLEC9A+ human DC is provided as well as their function in an immune reaction. Functionally, BDCA3+ CLEC9A+ DC are potent producers of IFN␥ and are thus considered to play an important role in anti-viral defense. Recent evidence indicated as well that they influence the polarization of naïve CD4+ T cells towards Th1 or Th2 cells and are capable of cross presentation. Sun Jung Kim and Betty Diamond’s review “Modulation of tolerogenic dendritic cells and autoimmunity” summarizes our current understanding on how DC subset formation and function is regulated. DC are critical regulators of the immune system and the two major functional outcomes mediated by DC being either immunogenic or tolerogenic. Inflammatory DC are formed transiently in response to an infection or extrinsic environmental stimuli and secrete several pro-inflammatory cytokines. Depending on the signals received, different inflammatory DC subtypes develop. In contrast, tolerogenic DC induce tolerance by dampening T cell activation either by directly interacting with CD8+ T cells, or inducing T regulatory cells. Regulation of the balance between induction of inflammation and tolerance must be tightly controlled. The intrinsic mechanisms that control immunogenic and tolerogenic DC function are mapped out together with the role of these subsets in autoimmunity. Finally, similarities and differences between mouse and human DC are highlighted. Mathew Collin, Muzlifah and Venetia Bigley review in “Human mononuclear phagocyte systems reunited” the phagocytic network
2
Editorial / Seminars in Cell & Developmental Biology 41 (2015) 1–2
that includes DC, monocytes and macrophages. Despite exerting highly similar effector functions, antigen processing and presentation, these three heterogeneous subsets in fact represent different cell types and discrimination between them has led to some confusion and discussion in the field. This review gives a comprehensive summary of the recent developments in the classification of human and mouse mononuclear phagocytes. In addition, the developmental origins of the different subsets are described in detail as well as the factors controlling maturation of these cells. Finally, the effector functions of the different subsets at steady state and during inflammation are highlighted.
The DC network in mouse and human is surprisingly heterogeneous and the regulation of different and highly specific DC subtypes highly complex. Despite this, our knowledge of the function of these cells within the immune system and the processes that regulate the specification of different populations is increasing rapidly. This collection by key leaders in the DC field aims to bring light the labyrinth of DC subsets in mouse and man and to summarize the most recent findings in DC biology.
Contents lists available at ScienceDirect
Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb
Editorial
In 1973, Ralph Steinman and Zanvil Cohn looked through a phase contrast microscope and discovered a cell type that was elongated and exhibited tree-like processes that were continually developing and contracting (Steinman and Cohn, 1973). This special accessory cell, named dendritic cell (DC) from the Greek word dendreon, set Steinman on a pathway spanning several decades to uncover that these cells were critical for processing and presenting antigens – a proposal met with considerable skepticism initially. In 2011, the intuitive insights of Steinman and Cohn and their research teams was awarded the Nobel Prize for Physiology or Medicine recognizing the transformative impact of their discovery in immunology and medicine. DC were shown to be responsible to prime the adaptive immune system, to influence the innate immune response and to have the ability to induce self-tolerance. To exert all these different functions, several specialized DC subsets have been found to exist and these often have tissue-specific localizations. This special review edition is composed of seven reviews which address several key aspects of DC biology including the definition of DC as a lineage, mouse and human DC development and the role of DC in tolerance induction and autoimmunity: In the first review, “Towards defining a lineage – The case for dendritic cells” by Leila Perie and Shalin Naik, the origin of DC subsets is discussed. All DC subsets arise from hematopoietic stem cells. Mature hematopoietic lineages are subdivided in lymphoid and myeloid-erythroid lineage. Lymphoid cells develop from a common lymphoid progenitor that has lost myeloid-erythroid lineage potential and comprises of T, B and innate lymphoid cells. Myeloiderythroid cell types derive from a common myeloid progenitor that has lost all lymphoid potential. Interestingly, DC are unique within the hematopoietic system in that they can arise from the lymphoid as well as the myeloid arm, indicating that DC subtypes could be considered as different lineages if the origin of a cell is used for the definition of a lineage. This review summarizes the recent data on DC development through the use of several lineage tracing techniques and propose an “overlap” model of lineage commitment. In “Dendritic cells and monocyte derived cells: two complementary and integrated functional systems”, Andreas Schlitzer, Naomi McGovern and Florent Ginhoux discuss the differences and similarities between DC and monocyte-derived cells (MC). The majority of DC, named conventional DC (cDC), derive from a common precursor and do not arise from monocytes. However, “inflammatory” DC are not present in the steady state but differentiate from monocytes during infection/inflammation. This review summarizes the latest findings of the organization of DC and MCs networks.
http://dx.doi.org/10.1016/j.semcdb.2015.05.010 1084-9521/© 2015 Published by Elsevier Ltd.
Two reviews focus on the skin and resident DC subtype, the Langerhans cells (LCs). LCs are a highly specialized DC subset and differ in their origin and molecular make up from the other DC subtypes. In “Establishing and maintaining the Langerhans cell network” Michael Chopin and Stephen Nutt describe the extrinsic and intrinsic mechanisms that govern LC lineage fate and function. The different developmental origins of LCs are discussed as well as the transcriptional network that governs LC identity. Thomas Hieronymus, Martin Zenke, Jea-Hyun-Baek and Kristin Sere address in “The clash of Langerhans cell homeostasis in skin: should I stay or should I go” the importance of certain receptor kinases in LC development and the role of epithelial-to-mesenchymal-transition and mesenchymal-to-epithelial-transition in the LC life cycle. In “BDCA3+ CLEC9A+ human dendritic cell function and development” by Evelyn van der Aa, Nadine van Montfort and Andrea Woltman, the authors give a comprehensive review of the newly identified human BDCA3+ CLEC9A+ human DC subset which are thought to be the human counterpart to mouse CD8␣+ and CD103+ DC. A detailed phenotypic description of BDCA3+ CLEC9A+ human DC is provided as well as their function in an immune reaction. Functionally, BDCA3+ CLEC9A+ DC are potent producers of IFN␥ and are thus considered to play an important role in anti-viral defense. Recent evidence indicated as well that they influence the polarization of naïve CD4+ T cells towards Th1 or Th2 cells and are capable of cross presentation. Sun Jung Kim and Betty Diamond’s review “Modulation of tolerogenic dendritic cells and autoimmunity” summarizes our current understanding on how DC subset formation and function is regulated. DC are critical regulators of the immune system and the two major functional outcomes mediated by DC being either immunogenic or tolerogenic. Inflammatory DC are formed transiently in response to an infection or extrinsic environmental stimuli and secrete several pro-inflammatory cytokines. Depending on the signals received, different inflammatory DC subtypes develop. In contrast, tolerogenic DC induce tolerance by dampening T cell activation either by directly interacting with CD8+ T cells, or inducing T regulatory cells. Regulation of the balance between induction of inflammation and tolerance must be tightly controlled. The intrinsic mechanisms that control immunogenic and tolerogenic DC function are mapped out together with the role of these subsets in autoimmunity. Finally, similarities and differences between mouse and human DC are highlighted. Mathew Collin, Muzlifah and Venetia Bigley review in “Human mononuclear phagocyte systems reunited” the phagocytic network
2
Editorial / Seminars in Cell & Developmental Biology 41 (2015) 1–2
that includes DC, monocytes and macrophages. Despite exerting highly similar effector functions, antigen processing and presentation, these three heterogeneous subsets in fact represent different cell types and discrimination between them has led to some confusion and discussion in the field. This review gives a comprehensive summary of the recent developments in the classification of human and mouse mononuclear phagocytes. In addition, the developmental origins of the different subsets are described in detail as well as the factors controlling maturation of these cells. Finally, the effector functions of the different subsets at steady state and during inflammation are highlighted.
The DC network in mouse and human is surprisingly heterogeneous and the regulation of different and highly specific DC subtypes highly complex. Despite this, our knowledge of the function of these cells within the immune system and the processes that regulate the specification of different populations is increasing rapidly. This collection by key leaders in the DC field aims to bring light the labyrinth of DC subsets in mouse and man and to summarize the most recent findings in DC biology.
