Lung development and emerging roles for type 2 immunity

Lung development is a complex process mediated through the interaction of multiple cell types, factors and mediators. In mice, it starts as early as embryonic day 9 and continues into early adulthood. The process can be separated into five different developmental stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. Whilst lung bud formation and branching morphogenesis have been studied extensively, the mechanisms of alveolarisation are incompletely understood. Aberrant lung development can lead to deleterious consequences for respiratory health such as bronchopulmonary dysplasia (BPD), a disease primarily affecting preterm neonates, which is characterised by increased pulmonary inflammation and disturbed alveolarisation. While the deleterious effects of type 1-mediated inflammatory responses on lung development have been well established, the role of type 2 responses in postnatal lung development remains poorly understood. Recent studies indicate that type 2-associated immune cells, such as group 2 innate lymphoid cells and alveolar macrophages, are increased in number during postnatal alveolarisation. Here, we present the current state of understanding of the postnatal stages of lung development and the key cell types and mediators known to be involved. We also provide an overview of how stem cells are involved in lung development and regeneration, and the negative influences of respiratory infections. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Are rats more human than mice?

In contrast to rats, mouse models are nowadays generally used for the investigation of immune responses and immune-mediated diseases, there are many different strains and mouse-specific tools available, and it is easy to generate transgenic and constitutive or inducible knockout mice for any gene. Many immune markers and mechanisms have been detected in mice and have been introduced as gold standard in immunology, however, some turned out to be not unconditionally transferable to the human immune system.Rats have been used more frequently in former days but are mostly outstripped by mice due to the fact that fewer strains are available, they need more space than mice, are more expensive to maintain and breed, and it is extremely difficult to generate transgenic or ko-rats. Consequently, the choice of rat-specific diagnostic tools like antibodies is quite poor and most researchers have switched to mouse models for the investigation of immune mechanisms, while rats are still widely used for toxicology by the pharmaceutical industry. However, it should be taken into consideration that there are some immunological similarities between rats and humans that are not presented in mice. Some of them like MHC class II and Foxp3 expression by activated effector T cells we have detected during our research on the immune response of rat models of experimental autoimmune uveitis.     

Immunobiology of chimeric antigen receptor T cells and novel designs

Advances in the development of immunotherapies have offered exciting new options for the treatment of malignant diseases that are refractory to conventional cytotoxic chemotherapies. The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated dramatic results in clinical trials and highlights the promise of novel immune‐based approaches to the treatment of cancer. As experience with CAR T cells has expanded with longer follow‐up and to a broader range of diseases, new obstacles have been identified which limit the potential lifelong benefits of CAR T cell therapy. These obstacles highlight not only the gaps in knowledge of the optimal clinical application of this “living drug”, but also gaps in our understanding of the fundamental biology of CAR T cells themselves. In this review, we discuss the obstacles facing CAR T cell therapy, how these relate to our current understanding of CAR T cell biology and approaches to enhance the clinical efficacy of this therapy.     

The emerging role of regulatory T cells following lung transplantation

Regulatory T cells (Treg) have proven to be a powerful immunologic force in nearly every organ system and hold therapeutic potential for a wide range of diseases. Insights gained from non‐transplant pathologies, such as infection, cancer, and autoimmunity, are now being translated to the field of solid organ transplantation, particularly for livers and kidneys. Recent insights from animal models of lung transplantation have established that Tregs play a vital role in suppressing rejection and facilitating tolerance of lung allografts, and such discoveries are being validated in human studies and preclinical trials. Given that long‐term outcomes following lung transplantation remain profoundly limited by chronic rejection, Treg therapy holds the potential to significantly improve patient outcomes and should be aggressively investigated.     

Germinal center B cell initiation,GC maturation,and the coevolution of its stromal cell niches

Throughout the developing GC response, B cell survival and fate choices made at the single cell level are dependent on signals received largely through interactions with other cells, often with cognate T cells. The type of signals that a given B cell can encounter is dictated by its location within tissue microarchitecture. The focus of this review is on the initiation and evolution of the GC response at the earliest time points. Here, we review the key factors influencing the progression of GC B cell differentiation that are both stage and context dependent. Finally, we describe the coevolution of niches within and surrounding the GC that influence the outcome of the GC response.