B and T lymphocytes are the mediators of immunity, but their function is under the control of dendritic cells. Dendritic cells in the periphery capture and process antigens, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. They not only activate lymphocytes, they also tolerize T cells to antigens that are innate to the body (self-antigens), thereby minimizing autoimmune reactions. Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis. With knowledge comes the realization that these cells are a powerful tool for manipulating the immune system.

Dendritic cells and the control of immunity

Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.

Immunobiology of Dendritic Cells

Dendritic cells (DCs) collect and process antigens for presentation to T cells, but there are many variations on this basic theme. DCs differ in the regulatory signals they transmit, directing T cells to different types of immune response or to tolerance. Although many DC subtypes arise from separate developmental pathways, their development and function are modulated by exogenous factors. Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground.

Mouse and human dendritic cell subtypes

Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.

Taking dendritic cells into medicine

Dendritic cells (DCs) form a remarkable cellular network that shapes adaptive immune responses according to peripheral cues. After four decades of research, we now know that DCs arise from a hematopoietic lineage distinct from other leukocytes, establishing the DC system as a unique hematopoietic branch. Recent work has also established that tissue DCs consist of developmentally and functionally distinct subsets that differentially regulate T lymphocyte function. This review discusses major advances in our understanding of the regulation of DC lineage commitment, differentiation, diversification, and function in situ.

The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting.

Human dendritic cells (DC) can now be generated in vitro in large numbers by culturing CD34+ hematopoietic progenitors in presence of GM-CSF+TNF alpha for 12 d. The present study demonstrates that cord blood CD34+ HPC indeed differentiate along two independent DC pathways. At early time points (day 5-7) during the culture, two subsets of DC precursors identified by the exclusive expression of CD1a and CD14 emerge independently. Both precursor subsets mature at day 12-14 into DC with typical morphology and phenotype (CD80, CD83, CD86, CD58, high HLA class II). CD1a+ precursors give rise to cells characterized by the expression of Birbeck granules, the Lag antigen and E-cadherin, three markers specifically expressed on Langerhans cells in the epidermis. In contrast, the CD14+ progenitors mature into CD1a+ DC lacking Birbeck granules, E-cadherin, and Lag antigen but expressing CD2, CD9, CD68, and the coagulation factor XIIIa described in dermal dendritic cells. The two mature DC were equally potent in stimulating allogeneic CD45RA+ naive T cells. Interestingly, the CD14+ precursors, but not the CD1a+ precursors, represent bipotent cells that can be induced to differentiate, in response to M-CSF, into macrophage-like cells, lacking accessory function for T cells. Altogether, these results demonstrate that different pathways of DC development exist: the Langerhans cells and the CD14(+)-derived DC related to dermal DC or circulating blood DC. The physiological relevance of these two pathways of DC development is discussed with regard to their potential in vivo counterparts.

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CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha.

BACKGROUND
Familial involvement in the neonatal intensive care unit (NICU) reduces parental stress and strengthens parental-infant bonding. However, parents often face barriers to in-person visitation. The coronavirus disease-2019 COVID-19 pandemic has exacerbated limitations to parental bedside presence.


OBJECTIVE
To design, implement, and evaluate a technology-based program to connect NICU babies with their families during the COVID-19 pandemic.


METHODS
We created NeoConnect at our level IV NICU, which included parental audio recordings and video chats between parents and their babies. Parental and NICU staff input on NeoConnect was gathered via preimplementation surveys. Inaugural families and staff members completed a postparticipation survey.


RESULTS
Prior to implementation, all parents who were surveyed (n = 24) wished they could be more involved in their baby's care. In the first 3 months of NeoConnect, 48 families participated in the audio recording project and 14 families participated in the video chat initiative. Following implementation, 85% of surveyed staff (28/33) reported that the patients became calmer when listening to their parents' recorded voice and 100% of surveyed parents (6/6) reported that video chats reduced their stress level.


CONCLUSION
Harnessing technology as a tool to increase parental involvement in the NICU is feasible and beneficial for NICU patients and their families.

NeoConnect: The Design, Implementation, and Impact of a Virtual Family-Centered NICU Program.

Background: Familial involvement in the neonatal intensive care unit (NICU) reduces parental stress and strengthens parental-infant bonding. However, parents often face barriers to in-person visitation. The coronavirus disease-2019 COVID-19 pandemic has exacerbated limitations to parental bedside presence. Objective: To design, implement, and evaluate a technology-based program to connect NICU babies with their families during the COVID-19 pandemic. Methods: We created NeoConnect at our level IV NICU, which included parental audio recordings and video chats between parents and their babies. Parental and NICU staff input on NeoConnect was gathered via preimplementation surveys. Inaugural families and staff members completed a postparticipation survey. Results: Prior to implementation, all parents who were surveyed (n = 24) wished they could be more involved in their baby's care. In the first 3 months of NeoConnect, 48 families participated in the audio recording project and 14 families participated in the video chat initiative. Following implementation, 85% of surveyed staff (28/33) reported that the patients became calmer when listening to their parents' recorded voice and 100% of surveyed parents (6/6) reported that video chats reduced their stress level. Conclusion: Harnessing technology as a tool to increase parental involvement in the NICU is feasible and beneficial for NICU patients and their families.

C Jacquet

Papers

CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha.

NeoConnect: The Design, Implementation, and Impact of a Virtual Family-Centered NICU Program.

NeoConnect