DC1

Dendritic cells (DCs) are a unique class of immune cells that act as a bridge between innate and adaptive immunity. The discovery of DCs by Cohen and Steinman in 1973 laid the foundation for DC biology, and the advances in the field identified different versions of DCs with unique properties and functions. DCs originate from hematopoietic stem cells, and their differentiation is modulated by Flt3L. They are professional antigen-presenting cells that patrol the environmental interphase, sites of infection, or infiltrate pathological tissues looking for antigens that can be used to activate effector cells. DCs are critical for the initiation of the cellular and humoral immune response and protection from infectious diseases or tumors. DCs can take up antigens using specialized surface receptors such as endocytosis receptors, phagocytosis receptors, and C type lectin receptors. Moreover, DCs are equipped with an array of extracellular and intracellular pattern recognition receptors for sensing different danger signals. Upon sensing the danger signals, DCs get activated, upregulate costimulatory molecules, produce various cytokines and chemokines, take up antigen and process it and migrate to lymph nodes where they present antigens to both CD8 and CD4 T cells. DCs are classified into different subsets based on an integrated approach considering their surface phenotype, expression of unique and conserved molecules, ontogeny, and functions. They can be broadly classified as conventional DCs consisting of two subsets (DC1 and DC2), plasmacytoid DCs, inflammatory DCs, and Langerhans cells.

Tumor-infiltrating dendritic cells (DCs) assume varied functional states that impact anti-tumor immunity. To delineate the DC states associated with productive anti-tumor T cell immunity, we compared spontaneously regressing and progressing tumors. Tumor-reactive CD8 + T cell responses in Batf3 -/- mice lacking type 1 DCs (DC1s) were lost in progressor tumors but preserved in regressor tumors. Transcriptional profiling of intra-tumoral DCs within regressor tumors revealed an activation state of CD11b + conventional DCs (DC2s) characterized by expression of interferon (IFN)-stimulated genes (ISGs) (ISG + DCs). ISG + DC-activated CD8 + T cells ex vivo comparably to DC1. Unlike cross-presenting DC1, ISG + DCs acquired and presented intact tumor-derived peptide-major histocompatibility complex class I (MHC class I) complexes. Constitutive type I IFN production by regressor tumors drove the ISG + DC state, and activation of MHC class I-dressed ISG + DCs by exogenous IFN-β rescued anti-tumor immunity against progressor tumors in Batf3 -/- mice. The ISG + DC gene signature is detectable in human tumors. Engaging this functional DC state may present an approach for the treatment of human disease.

The diaphragm is the primary muscle of ventilation. Dysfunction of the diaphragm is an underappreciated cause of respiratory difficulties and may be due to a wide variety of entities, including surgery, trauma, tumor, and infection. Diaphragmatic disease usually manifests as elevation at chest radiography. Functional imaging with fluoroscopy (or ultrasonography or magnetic resonance imaging) is a simple and effective method of diagnosing diaphragmatic dysfunction, which can be classified as paralysis, weakness, or eventration. Diaphragmatic paralysis is indicated by absence of orthograde excursion on quiet and deep breathing, with paradoxical motion on sniffing. Diaphragmatic weakness is indicated by reduced or delayed orthograde excursion on deep breathing, with or without paradoxical motion on sniffing. Eventration is congenital thinning of a segment of diaphragmatic muscle and manifests as focal weakness. Treatment of diaphragmatic paralysis depends on the cause of the dysfunction and the severity of the symptoms. Treatment options include plication and phrenic nerve stimulation. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.322115127/-/DC1.