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Innate lymphoid cells type 2 (ILC2) are considered the innate counterpart of Th2 cells and cooperate with them in host protection against helminths and in the pathogenesis of allergic diseases. ILC2 are characterized by type 2 cytokines production (IL-13, IL-4 and IL-5) and by GATA-3 transcription factor expression. Belonging to innate immune system, ILC2 lack of antigen specific receptor and their activation is controlled mainly by epithelial derived cytokines, such as TSLP, IL-25, and IL-33. ILC2 are located in a strategic position in the airway mucosa and are important to patrol the airways, to recruit other immune system cells and to activate resident cells in response to pathogens injury and/or tissue damage. In the last decade, many studies, in both humans and mice, focused on ILC2, fully investigating their main features such as the development from the precursor, the stimuli for their activation or inhibition, their plasticity, their classification in different subsets, and finally, their pathogenetic role in type 2 immune-mediated disorders. In this review we performed an excursus on phenotypical and functional properties on both human and mouse ILC2, in physiological and pathological conditions (mainly in type 2 asthma), considering this cell subset as target for specific therapeutic strategies. [ABSTRACT FROM AUTHOR]

• Sarcina Ventriculi is mainly isolated in the gastrointestinal tract. • Upper endoscopy could lead to SV diagnosis and rule out gastric perforations • Antibiotic therapy may eradicate the infection and prevent complications. • Emergency surgery is required in case of source control. This study is aimed to report a case of SV -related gastritis and the results of a systematic literature review of SV infections. Following a case presentation, we systematically searched different databases (MEDLINE, PubMed, Scopus, Web of Science, EMBASE, google scholar) for the items " sarcina, " " ventriculi, " " clostridium " with AND/OR. A total of 55 articles reporting 65 cases of Sarcina Ventriculi were found. Thus, 66 patients, including our case, were reviewed. The median age was 51 years (IQR: 0-87 years). Females accounted for 51% of cases. 68% of patients had one or more comorbidities. SV was isolated in the gastrointestinal tract (88%), respiratory (5%), urine (4%), and bloodstream (3%) systems. Upper endoscopy was performed in 52 patients (79%). Biopsies were obtained in all 52 cases and were normal in 23%. Surgery was warranted in 15 patients (23%), and specific antimicrobial therapy was delivered in 34 (52%) patients. Mortality was 14%. At follow-up, 88% of patients showed complete eradication of the SV infection. Upper gastrointestinal biopsy positive for SV should prompt an evaluation of the clinical conditions, considering the risk of gastric perforation is not negligible. Antibiotic therapy may eradicate the infection and prevent complications. Emergency surgery is required in case of source control. [ABSTRACT FROM AUTHOR]

• Human circulating ILC2 are modulated versus type 1 and type 3. • Modulated ILC2 showed reduced abilty to induce IgE production by B cells. • Treg cells reduced ILC2 proliferation and their CD154 expression. Human group 2 innate lymphoid cells (ILC2) represent the innate counterpart of Th2 cells and cooperate with them in helminths protection and in the pathogenesis of allergic diseases. Some reports described ILC2 plasticity and few studies investigated the cellular and molecular mechanisms regulating human ILC2 functions. The aim of this study is to define how immune deviation and immune regulation control human ILC2-mediated immune response. Human circulating ILC2 were expanded in vitro and then cultured in presence of IL-12 or IL-1β plus IL-23 or co-coltured in presence of circulating CD4+CD25highFoxp3+Treg. IL-12 induces IFN-γ production and upregulation of T-bet mRNA level on human circulating ILC2 whereas IL-1β and IL-23 mediate IL-22 production and upregulation of RORC mRNA level. In all these conditions, GATA-3 mRNA level is not reduced and the typical type 2 cytokines are only partially reduced. Moreover, "modulated" ILC2 have reduced ability to induce IgE producing by B cells. ILC2 proliferation, cytokines production and CD154 expression were inhibited by CD4+CD25highFoxp3+ Treg cells. TGF-β reduced CD154 expression on ILC2 stimulated with IL-25/IL-33. This study defines possible cellular and molecular mechanisms responsible for modulation and inhibition of human ILC2 activity. These results may be useful in the development of strategies aimed to dampen ILC2 function in type-2 mediated diseases. [ABSTRACT FROM AUTHOR]

Background Protection against helminths consists of adaptive responses by T H 2 cells and innate responses by group 2 innate lymphoid cells (ILC2s), with these latter being well characterized in mice but less so in human subjects. Objective We sought to characterize human circulating ILC2s and compare their functional profile with that of autologous T H 2 cells. Methods Circulating ILC2s and T H 2 cells were isolated by means of fluorescence-activated cell sorting and magnetic cell sorting and expanded in vitro . ILC2s were then stimulated with phorbol 12-myristate 13-acetate plus ionomycin, IL-25 plus IL-33 (IL-25/IL-33), or a mixture of Toll-like receptor ligands to evaluate their ability to produce cytokines, express CD154, and induce IgE production by autologous B cells. Cytokines and transcription factor gene methylation were assessed. Results ILC2s expressed GATA-3, retinoic acid orphan receptor (RORC) 2, and RORα; were able to produce IL-5, IL-13, and IL-4; and, accordingly, were characterized by demethylation of IL4 , IL13 , IL5 , GATA3 , and RORC2 , whereas the IFNG , IFNG promoter, and TBX21 regions of interest were methylated. ILC2s expressed TLR1 , TLR4 , and TLR6 , and TLR stimulation induced IL-5 and IL-13 production. Moreover, ILC2s expressed CD154 in response to phorbol 12-myristate 13-acetate plus ionomycin, IL-25/IL-33, or a mixture of TLR ligands. Stimulated ILC2s also induced IgM, IgG, IgA, and IgE production by B cells. Finally, circulating ILC2s from atopic patients were not different in numbers and frequency but expressed higher IL-4 levels than those from nonatopic subjects. Conclusion This study provides the first evidence that human ILC2s can express CD154 and stimulate the production of IgE by B lymphocytes through IL-25/IL-33 stimulation or TLR triggering. [ABSTRACT FROM AUTHOR]

• IL-6 has a central role in COVID-19 cytokine storm and into the promotion of coagulation thus exerting prothrombotic effect. • Tocilizumab improved the alveolar-arterial oxygen gradient and the vascular radiologic score at 1 week after treatment. • By blocking the IL-6 axis tocilizumab may improve lung perfusion in patients with severe COVID-19 pneumonia. As of October 2020 management of Coronavirus disease 2019 (COVID-19) is based on supportive care and off-label or compassionate-use therapies. On March 2020 tocilizumab - an anti-IL-6 receptor monoclonal antibody - was suggested as immunomodulatory treatment in severe COVID-19 because hyperinflammatory syndrome occurs in many patients similarly to the cytokine release syndrome that develops after CAR-T cell therapy. In our retrospective observational study, 20 severe COVID-19 patients requiring intensive care were treated with tocilizumab in addition to standard-of-care therapy (SOC) and compared with 13 COVID-19 patients receiving only SOC. Clinical respiratory status, inflammatory markers and vascular radiologic score improved after one week from tocilizumab administration. On the contrary, these parameters were stable or worsened in patients receiving only SOC. Despite major study limitations, improvement of alveolar-arterial oxygen gradient as well as vascular radiologic score after one week may account for improved pulmonary vascular perfusion and could explain the more rapid recovery of COVID-19 patients receiving tocilizumab compared to controls. [ABSTRACT FROM AUTHOR]