A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

Dendritic cells (DCs) are important in regulating immunity and tolerance and consist of functionally distinct subsets that differentially regulate T lymphocyte function. The underlying basis for this subset specificity is lacking, particularly in humans, where the classification of tissue DCs is currently incomplete. Examination of healthy human epidermal Langerhans cells and dermal skin cells revealed a tissue CD5-expressing DC subtype. The CD5+ DCs were potent inducers of cytotoxic T cells and Th22 cells. The products of these T cells, IL-22 and IFN-γ, play a key role in the pathogenesis of psoriasis. Remarkably, CD5+ DCs were significantly enriched in lesional psoriatic skin compared with distal tissues, suggesting their involvement in the disease. We show that CD5+ DCs can be differentiated from hematopoietic progenitor cells independently of the CD5- DCs. A progenitor population found in human cord blood and in the dermal skin layer, marked as CD34-CD123+CD117dimCD45RA+, was an immediate precursor of these CD11c+CD1c+CD5+ DCs. Overall, our discovery of the CD5-expressing DC subtype suggests that strategies to regulate their composition or function in the skin will represent an innovative approach for the treatment of immune-mediated disorders in and beyond the skin

Cognitive rehabilitation and sensory functioning in old people with mild cognitive impairment

Introducción: Se presentan los resultados obtenidos tras la aplicación de un protocolo de rehabilitación cognitiva basado en el funcionamiento sensorial de personas mayores. Metodología: se trata de un estudio pre-post, en el que un grupo de 4 personas mayores de 55 años con deterioro cognitivo leve participa durante 5 semanas, 3 veces a la semana, 60 minutos cada sesión en un protocolo de rehabilitación cognitiva. Se evalúan los dominios cognitivos, la independencia en actividades instrumentales de la vida diaria y la percepción de la carga del cuidador. Se desarrollan las actividades en cinco etapas propuestas por Ross y Burdick, bajo los principios de integración sensorial. Resultados: Se evidencia el mantenimiento de habilidades como atención y función ejecutiva en dos de los participantes y un mejor desempeño cognitivo en las otras dos personas en áreas como la orientación, la memoria, la percepción, y las operaciones racionales; al igual que en la ejecución de actividades instrumentales de la vida diaria. Discusión: En Colombia son pocos los programas de rehabilitación cognitiva dirigidos a personas mayores, la evidencia muestra que dichos programas generan resultados en la independencia cotidiana, en las relaciones y en el entorno socio-familiar. Se hace necesario aumentar el tiempo de ejecución del protocolo ya que podrían evidenciarse mejores resultados en los dominios anteriormente descritos. Hay una escasa producción académica alrededor del uso de los principios de integración sensorial en los programas de rehabilitación cognitiva, lo que amerita el trabajo por parte de terapeutas ocupacionales en lainvestigación sobre este temaIntroduction: We present the results obtained after the application of a cognitive rehabilitation protocol based on sensory functioning of elderly. Methodology: this is a pre-post study, in which a group of 4 people over 55 years with mild cognitive impairment participated for 5 weeks,3timesa week, 60 minutes each session in a cognitive rehabilitation protocol. It assesses the cognitive domains, independence in instrumental activities of daily living and caregiver s perceived burden. Activities are developed in five stages proposed by Ross and Burdick , under the principles of sensory integration. Results: there are evidence about the maintaining of the attention and the executive function in two of the participants and better cognitive performance in the other two people in the areas of orientation, memory, perception, and rational operations, as in the performance of instrumental activities of daily living. Discussion: In Colombia there are few cognitive rehabilitation programs for older people, the evidence shows that these programs generate results in daily independence, relationships and the social and family environment. It is necessary to increase the protocol execution time because it could show best performance in the domains described above. There is little academic production around the use of sensory integration principles in cognitive rehabilitation programs, which justi!es the work by occupational therapists in research on this topic

Modular expression analysis reveals functional conservation between human Langerhans cells and mouse cross-priming dendritic cells

Characterization of functionally distinct dendritic cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were used for defining shared functions between the species. Comparing modules derived from four human skin DC subsets and modules derived from the Immunological Genome Project database for all mouse DC subsets revealed that human Langerhans cells (LCs) and the mouse XCR1(+)CD8α(+)CD103(+) DCs shared the class I-mediated antigen processing and cross-presentation transcriptional modules that were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting CD141/BDCA-3(+) DCs, the proposed equivalent to mouse CD8α(+) DCs. Consistent with our analysis, LCs were highly adept at inducing primary CTL responses. Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target

Differential IRF8 Transcription Factor Requirement Defines Two Pathways of Dendritic Cell Development in Humans

The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8. Loss of IRF8 exerts a differential effect on DC subsets, including plasmacytoid DCs (pDCs) and the classical DC lineages cDC1 and cDC2. In humans, cDC2-related subsets have been described including AXL+ SIGLEC6+ pre-DC, DC2 and DC3. The origin of this heterogeneity is unknown. Using highdimensional analysis, in vitro differentiation, and an allelic series of human IRF8 deficiency, we demonstrated that cDC2 (CD1c+ DC) heterogeneity originates from two distinct pathways of development. The lymphoidprimed IRF8hi pathway, marked by CD123 and BTLA, carried pDC, cDC1, and DC2 trajectories, while the common myeloid IRF8lo pathway, expressing SIRPA, formed DC3s and monocytes. We traced distinct trajectories through the granulocyte-macrophage progenitor (GMP) compartment showing that AXL+ SIGLEC6+ pre-DCs mapped exclusively to the DC2 pathway. In keeping with their lower requirement for IRF8, DC3s expand to replace DC2s in human partial IRF8 deficiency

Gustatory innervation and bax -dependent Caspase-2: Participants in the life and death pathways of mouse taste receptor cells

In the adult mouse tongue, an average of 11% of the gustatory receptor cells are replaced each day. In investigating homeostatic cell death mechanisms in gustatory renewing epithelium, we observed that taste receptor cells were selectively immunopositive for the bcl-2 family death factor, Bax, and for the protease Caspase-2 Nedd2/Ich1 . We determined that 8–10% of the taste receptor cells of the vallate papilla were Bax positive and that 11% were Caspase-2 positive. Some of these immunopositive taste cells had apoptotic morphological defects. Within the subset of vallate taste cells immunopositive for either Caspase-2 or Bax, up to 79% coexpressed both death factors. Bax and Caspase-2 first appeared in occasional vallate taste receptor cells on the same postnatal day—the day after birth. bax null mutation markedly reduced gustatory Caspase-2 immunoexpression. These observations suggest that taste cell death pathways utilize p53, Bax, and Caspase-2 to dispose of aged receptor cells. Apart from reducing Caspase-2 expression, Bax deficiency also altered taste organ development. bax −/− mice had a more profusely innervated vallate papilla, which grew to be 25% longer and taller, with the mean taste bud containing more than twice the normal number of taste cells. This augmentation of taste organ development with increased innervation is complementary to the well-documented reduction in taste organ development with sparse innervation. We propose that additional taste neurons survived programmed cell death in Bax-deficient mice, thereby providing an inductive boost to vallate gustatory development. J. Comp. Neurol. 424:640–650, 2000. © 2000 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34462/1/6_ftp.pd

Liberating Voices

Troubling Violence: A Performance Project, by M. Heather Carver and Elaine J. Lawless. Jackson: University Press of Mississippi, 2009. Hardback $50.00; paperback$25.00