Cell-based therapy in prophylaxis and treatment of chronic graft-versus-host disease

Copyright © 2022 Doglio, Crossland, Alho, Penack, Dickinson, Stary, Lacerda, Eissner and Inngjerdingen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Hematopoietic allogeneic stem cell transplantation (allo-SCT) is a curative option for patients with hematological malignancies. However, due to disparities in major and minor histocompatibility antigens between donor and recipient, severe inflammatory complications can occur, among which chronic graft-versus-host disease (cGVHD) can be life-threatening. A classical therapeutic approach to the prevention and treatment of cGVHD has been broad immunosuppression, but more recently adjuvant immunotherapies have been tested. This review summarizes and discusses immunomodulatory approaches with T cells, including chimeric antigen receptor (CAR) and regulatory T cells, with natural killer (NK) cells and innate lymphoid cells (ILCs), and finally with mesenchymal stromal cells (MSC) and extracellular vesicles thereof. Clinical studies and pre-clinical research results are presented likewise.This work was supported by COST (European Cooperation in Science and Technology). www.cost.eu - COST Action 17138 EUROGRAFT.info:eu-repo/semantics/publishedVersio

PReS-FINAL-2232: Long-term follow-up in a national cohort of MKD patients: search for clinical predictors of a spontaneous improvement

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Translational implications of Th17-skewed inflammation due to genetic deficiency of a cadherin stress sensor

Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions and multiple allergies, and isolated patient keratinocytes exhibit increased proallergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the 3 tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1–/– skin showed a delay in expression of adhesion/differentiation/ keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17–skewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1–/– mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of 2 Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth, and treatment with a targeted therapy significantly improved skin lesions in patients

Osteological peculiarities of Bufo brongersmai (Anura: Bufonidae) and their possible relation to life in an arid environment

Osteological peculiarities of Bufo brongersmai (Anura: Bufonidae) and their possible relation to life in an arid environment. Zoological Studies 48(1): 108-119. The morphology of selected isolated skeletal elements of the northwestern African endemic toad Bufo brongersmai Hoogmoed 1972 is herein described and compared to those of other Bufo species inhabiting the same area and Europe. The osteological morphology of this species clearly differentiates it from others within the genus, and several diagnostic osteological characters are added to the specific diagnosis. In particular, the presence in adult individuals of a rather-large maxillary fontanella, which late in ontogeny is reduced to a few foramina, has not been observed in other species. These fontanellae, as well as the fenestrations on the sphenethmoid, together with other osteological traits, suggest a significant degree of hypo-ossification. This seems likely related to the rapid larval development that allows B. brongersmai to achieve higher reproductive fitness than other species in the highly ephemeral waters of the rocky, arid environment it inhabits. Other peculiar osteological traits could be related to the exploitation of small crevices to protect adults from overheating and desiccation

Primary red ear syndrome associated with cochleo-vestibular symptomatology: a paediatric case report.

Background Red ear syndrome (RES), first described by Lance in 1996 in an adult series, may be primary or associated with headache syndromes, upper cervical disorders or vascular anomalies. Clinically the disease is characterised by recurrent episodes of reddening and burning pain in the auricle, usually elicited by different triggers. The prevalence of RES in the paediatric age group remains poorly understood. Several therapeutic approaches have been tried with heterogeneous clinical response. Case results We report a paediatric patient suffering from primary RES associated with debilitating cochleo-vestibular symptomatology causing severe discomfort. Three years after the disease onset, the patient also developed headache, with clinical features of migraine. Discussion The temporal and spatial association could suggest shared pathogenetic features between neurological (cochleo-vestibular) and vascular (red and burning ear) symptomatology, likely related to trigeminal autonomic reflex activation, although further studies are required for full comprehension of RES pathogenesis. </jats:sec

New insights in systemic lupus erythematosus: from regulatory T cells to CAR-T-cell strategies

Systemic lupus erythematous is a heterogeneous autoimmune disease with potentially multiorgan damage. Its complex etiopathogenesis involves genetic, environmental, and hormonal factors, leading to a loss of self-tolerance with autoantibody production and immune complex formation. Given the relevance of autoreactive B lymphocytes, several therapeutic approaches have been made targeting these cells. However, the disease remains incurable, reflecting an unmet need for effective strategies. Novel therapeutic concepts have been investigated to provide more specific and sustainable disease modification compared with continued immunosuppression. Autologous hematopoietic stem cell transplantation has already provided the proof-of-concept that immunodepletion can lead to durable treatment-free remissions, albeit with significant treatment-related toxicity. In the future, chimeric antigen receptor-T-cell therapies, for example, CD19 chimeric antigen receptor-T, may provide a more effective lymphodepletion and with less toxicity than autologous hematopoietic stem cell transplantation. An emerging field is to enhance immune tolerance by exploiting the suppressive capacities of regulatory T cells, which are dysfunctional in patients with systemic lupus erythematous, and thus resemble promising candidates for adoptive cell therapy. Different approaches have been developed in this area, from polyclonal to genetically engineered regulatory T cells. In this article, we discuss the current evidence and future directions of cellular therapies for the treatment of systemic lupus erythematous, including hematopoietic stem cell transplantation and advanced regulatory T-cell–based cellular therapies

Inhibition of adhesion‐specific genes by Solidago virgaurea extract causes loss of Candida albicans biofilm integrity

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