IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.

BACKGROUND: Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5, and IL-13 cytokines produced by TH2 lymphocytes or type 2 innate lymphoid cells (ILC2s). IL-2 family cytokines play a key role in the differentiation, homeostasis, and effector function of innate and adaptive lymphocytes. OBJECTIVE: IL-9 and IL-21 boost activation and proliferation of TH2 and ILC2s, but the relative importance and potential synergism between these γ common chain cytokines are currently unknown. METHODS: Using newly generated antibodies, we inhibited IL-9 and IL-21 alone or in combination in various murine models of asthma. In a translational approach using segmental allergen challenge, we recently described elevated IL-9 levels in human subjects with allergic asthma compared with nonasthmatic controls. Here, we also measured IL-21 in both groups. RESULTS: IL-9 played a central role in controlling innate IL-33-induced lung inflammation by promoting proliferation and activation of ILC2s in an IL-21-independent manner. Conversely, chronic house dust mite-induced airway inflammation, mainly driven by adaptive immunity, was solely dependent on IL-21, which controlled TH2 activation, eosinophilia, total serum IgE, and formation of tertiary lymphoid structures. In a model of innate on adaptive immunity driven by papain allergen, a clear synergy was found between both pathways, as combined anti-IL-9 or anti-IL-21 blockade was superior in reducing key asthma features. In human bronchoalveolar lavage samples we measured elevated IL-21 protein within the allergic asthmatic group compared with the allergic control group. We also found increased IL21R transcripts and predicted IL-21 ligand activity in various disease-associated cell subsets. CONCLUSIONS: IL-9 and IL-21 play important and nonredundant roles in allergic asthma by boosting ILC2s and TH2 cells, revealing a dual IL-9 and IL-21 targeting strategy as a new and testable approach.

A Study of Zn-Ca Nanocomposites and Their Antibacterial Properties.

This study aimed to develop Ca2+ doped ZnO nanoparticles (NPs) and investigate their antibacterial properties against microorganisms of dental interest. Zn-Ca NPs were synthesized by the sol-gel method with different concentrations of Ca2+ (1, 3, and 5 wt. %) and subsequently characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-vis spectroscopy and Fourier transform infrared spectroscopy (FT-IR). The Kirby-Bauer method was used to measure antibacterial effects. NPs showed the wurzite phase of ZnO and bandgap energies (Eg) from 2.99 to 3.04 eV. SEM analysis showed an average particle size of 80 to 160 nm. The treatments that presented the best antibacterial activity were Zn-Ca 3% and Zn-Ca 5%. ZnO NPs represent an alternative to generate and improve materials with antibacterial capacity for dental applications.

Wound healing across the animal kingdom: Crosstalk between the immune system and the extracellular matrix.

Tissue regeneration is widespread in the animal kingdom. To date, key roles for different molecular and cellular programs in regeneration have been described, but the ultimate blueprint for this talent remains elusive. In animals capable of tissue regeneration, one of the most crucial stages is wound healing, whose main goal is to close the wound and prevent infection. In this stage, it is necessary to avoid scar formation to facilitate the activation of the immune system and remodeling of the extracellular matrix, key factors in promoting tissue regeneration. In this review, we will discuss the current state of knowledge regarding the role of the immune system and the interplay with the extracellular matrix to trigger a regenerative response.

Using transcriptomics to enable a plethodontid salamander (Bolitoglossa ramosi) for limb regeneration research.

BACKGROUND: Tissue regeneration is widely distributed across the tree of life. Among vertebrates, salamanders possess an exceptional ability to regenerate amputated limbs and other complex structures. Thus far, molecular insights about limb regeneration have come from a relatively limited number of species from two closely related salamander families. To gain a broader perspective on the molecular basis of limb regeneration and enhance the molecular toolkit of an emerging plethodontid salamander (Bolitoglossa ramosi), we used RNA-Seq to generate a de novo reference transcriptome and identify differentially expressed genes during limb regeneration. RESULTS: Using paired-end Illumina sequencing technology and Trinity assembly, a total of 433,809 transcripts were recovered and we obtained functional annotation for 142,926 non-redundant transcripts of the B. ramosi de novo reference transcriptome. Among the annotated transcripts, 602 genes were identified as differentially expressed during limb regeneration. This list was further processed to identify a core set of genes that exhibit conserved expression changes between B. ramosi and the Mexican axolotl (Ambystoma mexicanum), and presumably their common ancestor from approximately 180 million years ago. CONCLUSIONS: We identified genes from B. ramosi that are differentially expressed during limb regeneration, including multiple conserved protein-coding genes and possible putative species-specific genes. Comparative analyses reveal a subset of genes that show similar patterns of expression with ambystomatid species, which highlights the importance of developing comparative gene expression data for studies of limb regeneration among salamanders.

Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue.

Asthma is characterized by lung eosinophilia, remodeling, and mucus plugging, controlled by adaptive Th2 effector cells secreting IL-4, IL-5, and IL-13. Inhaled house dust mite (HDM) causes the release of barrier epithelial cytokines that activate various innate immune cells like DCs and basophils that can promote Th2 adaptive immunity directly or indirectly. Here, we show that basophils play a crucial role in the development of type 2 immunity and eosinophilic inflammation, mucus production, and bronchial hyperreactivity in response to HDM inhalation in C57Bl/6 mice. Interestingly, conditional depletion of basophils during sensitization did not reduce Th2 priming or asthma inception, whereas depletion during allergen challenge did. During the challenge of sensitized mice, basophil-intrinsic IL-33/ST2 signaling, and not FcεRI engagement, promoted basophil IL-4 production and subsequent Th2 cell recruitment to the lungs via vascular integrin expression. Basophil-intrinsic loss of the ubiquitin modifying molecule Tnfaip3, involved in dampening IL-33 signaling, enhanced key asthma features. Thus, IL-33-activated basophils are gatekeepers that boost allergic airway inflammation by controlling Th2 tissue entry.

Limb regeneration in salamanders: the plethodontid tale.

Salamanders are the only vertebrates that can regenerate limbs as adults. This makes them ideal models to investigate the cellular and molecular mechanisms of tissue regeneration. Ambystoma mexicanum and Nothopthalmus viridescens have long served as primary salamander models of limb regeneration, and the recent sequencing of the axolotl genome now provides a blueprint to mine regeneration insights from other salamander species. In particular, there is a need to study South American plethodontid salamanders that present different patterns of limb development and regeneration. A broader sampling of species using next-generation sequencing approaches is needed to reveal shared and unique mechanisms of regeneration, and more generally, the evolutionary history of salamander limb regeneration.

A de novo reference transcriptome for Bolitoglossa vallecula, an Andean mountain salamander in Colombia.

The amphibian order Caudata, contains several important model species for biological research. However, there is need to generate transcriptome data from representative species of the primary salamander families. Here we describe a de novo reference transcriptome for a terrestrial salamander, Bolitoglossa vallecula (Caudata: Plethodontidae). We employed paired-end (PE) illumina RNA sequencing to assemble a de novo reference transcriptome for B. vallecula. Assembled transcripts were compared against sequences from other vertebrate taxa to identify orthologous genes, and compared to the transcriptome of a close plethodontid relative (Bolitoglossa ramosi) to identify commonly expressed genes in the skin. This dataset should be useful to future comparative studies aimed at understanding important biological process, such as immunity, wound healing, and the production of antimicrobial compounds.

Recommendations of the Colombian Consensus Committee for the Management of Traumatic Brain Injury in Prehospital, Emergency Department, Surgery, and Intensive Care (Beyond One Option for Treatment of Traumatic Brain Injury: A Stratified Protocol [BOOTStraP]).

Background Traumatic brain injury (TBI) is a global public health problem. In Colombia, it is estimated that 70% of deaths from violence and 90% of deaths from road traffic accidents are TBI related. In the year 2014, the Ministry of Health of Colombia funded the development of a clinical practice guideline (CPG) for the diagnosis and treatment of adult patients with severe TBI. A critical barrier to the widespread implementation was identified-that is, the lack of a specific protocol that spans various levels of resources and complexity across the four treatment phases. The objective of this article is to present the process and recommendations for the management of patients with TBI in various resource environments, across the treatment phases of prehospital care, emergency department (ED), surgery, and intensive care unit. Methods Using the Delphi methodology, a consensus of 20 experts in emergency medicine, neurosurgery, prehospital care, and intensive care nationwide developed recommendations based on 13 questions for the management of patients with TBI in Colombia. Discussion It is estimated that 80% of the global population live in developing economies where access to resources required for optimum treatment is limited. There is limitation for applications of CPGs recommendations in areas where there is low availability or absence of resources for integral care. Development of mixed methods consensus, including evidence review and expertise points of good clinical practices can fill gaps in application of CPGs. BOOTStraP (Beyond One Option for Treatment of Traumatic Brain Injury: A Stratified Protocol) is intended to be a practical handbook for care providers to use to treat TBI patients with whatever resources are available. Results Stratification of recommendations for interventions according to the availability of the resources on different stages of integral care is a proposed method for filling gaps in actual evidence, to organize a better strategy for interventions in different real-life scenarios. We develop 10 algorithms of management for building TBI protocols based on expert consensus to articulate treatment options in prehospital care, EDs, neurological surgery, and intensive care, independent of the level of availability of resources for care.