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Journal of Immunology (Baltimore, Md. :... May 2020The adaptive immune system of all jawed vertebrates relies on the presence of B and T cell lymphocytes that aggregate in specific body sites to form primary and...
The adaptive immune system of all jawed vertebrates relies on the presence of B and T cell lymphocytes that aggregate in specific body sites to form primary and secondary lymphoid structures. Secondary lymphoid organs include organized MALT (-MALT) such as the tonsils and Peyer patches. -MALT became progressively organized during vertebrate evolution, and the TNF superfamily of genes has been identified as essential for the formation and maintenance of -MALT and other secondary and tertiary lymphoid structures in mammals. Yet, the molecular drivers of -MALT structures found in ectotherms and birds remain essentially unknown. In this study, we provide evidence that TNFSFs, such as lymphotoxins, are likely not a universal mechanism to maintain -MALT structures in adulthood of teleost fish, sarcopterygian fish, or birds. Although a role for TNFSF2 (TNF-α) cannot be ruled out, transcriptomics suggest that maintenance of -MALT in nonmammalian vertebrates relies on expression of diverse genes with shared biological functions in neuronal signaling. Importantly, we identify that expression of many genes with olfactory function is a unique feature of mammalian Peyer patches but not the -MALT of birds or ectotherms. These results provide a new view of -MALT evolution in vertebrates and indicate that different genes with shared biological functions may have driven the formation of these lymphoid structures by a process of convergent evolution.
Topics: Adaptive Immunity; Animals; B-Lymphocytes; Biological Evolution; Immunity, Mucosal; Lymphoid Tissue; Mucous Membrane; Neural Conduction; Palatine Tonsil; Peyer's Patches; T-Lymphocytes; Transcriptome; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Vertebrates
PubMed: 32238457
DOI: 10.4049/jimmunol.1901059 -
PloS One 2020Memory B cell (mBC) induction and maintenance is one of the keys to long-term protective humoral immunity. MBCs are fundamental to successful medical interventions such...
Human CD27+ memory B cells colonize a superficial follicular zone in the palatine tonsils with similarities to the spleen. A multicolor immunofluorescence study of lymphoid tissue.
BACKGROUND
Memory B cell (mBC) induction and maintenance is one of the keys to long-term protective humoral immunity. MBCs are fundamental to successful medical interventions such as vaccinations and therapy in autoimmunity. However, their lifestyle and anatomic residence remain enigmatic in humans. Extrapolation from animal studies serves as a conceptual basis but might be misleading due to major anatomical distinctions between species.
METHODS AND FINDINGS
Multicolor immunofluorescence stainings on fixed and unfixed frozen tissue sections were established using primary antibodies coupled to haptens and secondary signal amplification. The simultaneous detection of five different fluorescence signals enabled the localization and characterization of human CD27+CD20+Ki67- mBCs for the first time within one section using laser scanning microscopy. As a result, human tonsillar mBCs were initially identified within their complex microenvironment and their relative location to naïve B cells, plasma cells and T cells could be directly studied and compared to the human splenic mBC niche. In all investigated tonsils (n = 15), mBCs appeared to be not only located in a so far subepithelial defined area but were also follicle associated with a previous undescribed gradual decline towards the follicular mantle comparable to human spleen. However, mBC areas around secondary follicles with large germinal centers (GCs) in tonsils showed interruptions and a general widening towards the epithelium while in spleen the mBC-containing marginal zones (MZ) around smaller GCs were relatively broad and symmetrical. Considerably fewer IgM+IgD+/- pre-switch compared to IgA+ or IgG+ post-switch mBCs were detected in tonsils in contrast to spleen.
CONCLUSIONS
This study extends existing insights into the anatomic residence of human mBCs showing structural similarities of the superficial follicular area in human spleen and tonsil. Our data support the debate of renaming the human splenic MZ to 'superficial zone' in order to be aware of the differences in rodents and, moreover, to consider this term equally for the human palatine tonsil.
Topics: Adolescent; Adult; Aged; B-Lymphocytes; Cellular Microenvironment; Child; Germinal Center; Humans; Middle Aged; Palatine Tonsil; Spleen; Tumor Necrosis Factor Receptor Superfamily, Member 7
PubMed: 32187186
DOI: 10.1371/journal.pone.0229778 -
Age and Ageing Aug 2020Statins are widely prescribed in the treatment of hypercholesterolemia. While their efficacy in the secondary prevention of vascular events is proven, their safety...
Statins are widely prescribed in the treatment of hypercholesterolemia. While their efficacy in the secondary prevention of vascular events is proven, their safety profile in older patients with multiple co-morbidities and polypharmacy remains questionable. Although rare, antihydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is a severe adverse effect of statins, manifesting as myalgias, proximal muscle weakness, muscle cell necrosis and rhabdomyolysis. We report an uncommon case of an autopsy-proven anti-HMGCR necrotising myopathy predominately affecting pharyngeal muscles in an older patient, leading to dysphagia, pneumonia and death within 3 weeks from onset. Clinicians should screen for dysphagia in any patient with suspected anti-HMGCR myopathy, order an anti-HMGCR antibody titre and consider prompt immunosupressive therapy.
Topics: Aged; Autoantibodies; Autoimmune Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Myositis; Pharyngeal Muscles
PubMed: 32147707
DOI: 10.1093/ageing/afaa038 -
Acta Otorrinolaringologica Espanola 2020to review the modifications and advances in reconstructive surgery of the soft tissues of the oral cavity exclusively based on flaps that depend on the facial artery... (Review)
Review
INTRODUCTION
to review the modifications and advances in reconstructive surgery of the soft tissues of the oral cavity exclusively based on flaps that depend on the facial artery system.
METHODS
review of the literature regarding oral cavity reconstructions based on main facial artery system flaps.
DISCUSSION
The reconstruction of the soft tissues of the oral cavity, based on facial artery system flaps, offers satisfactory results and allows limited reconstructions avoiding the use of pedicled regional flaps or free flaps.
CONCLUSIONS
Knowledge of reconstructive options using the facial artery system in oral cavity surgery allows expanding reconstructive options for head and neck surgeons, enabling safe, high quality and effective reconstructions, with limited resources consumption.
Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Male; Maxillary Artery; Middle Aged; Mouth Neoplasms; Nasopharynx; Necrosis; Oral Fistula; Palate; Prospective Studies; Plastic Surgery Procedures; Respiratory Tract Fistula; Surgical Flaps; Surgical Wound Dehiscence; Treatment Outcome
PubMed: 32143840
DOI: 10.1016/j.otorri.2019.10.002 -
EBioMedicine Mar 2020Human immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in...
BACKGROUND
Human immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in secondary lymphoid organs, such as in the case of germinal center (GC) T follicular helper (Tfh) cells and GC B cells.
METHODS
We developed a versatile ex vivo lymphoid organ culture platform that is based on human pharyngeal tonsils (adenoids) and allows for drug testing. We systematically phenotyped Tfh and GC B cell subsets in explant- and suspension cultures using multicolor flow cytometry and cytokine multiplex analysis.
FINDINGS
Phenotypic changes of certain ex vivo cultured immune cell subsets could be modulated by cytokine addition. Furthermore, we optimized an activation-induced marker assay to evaluate the response to T cell stimulation. We provide proof-of-concept that Tfh and GC B cells could be modulated in these cultures by different anti-inflammatory drugs in unstimulated states and upon activation with vaccine-derived antigens. For example, GC B cells were lost upon CD40L blockade, and clinically approved JAK inhibitors impacted Tfh and GC B cells, including down-regulation of their key transcription factor BCL6. BCL6 regulation was affected by IL-6 signaling in T cells and IL-4 in B cells, respectively. Furthermore, we demonstrated that JAK signaling and TNF signaling contributed to the stimulation-induced activation of tonsil-derived T cells.
INTERPRETATION
Our optimized methods, assays, and mechanistic findings can contribute to a better understanding of human GC responses. These insights may be relevant for improving autoimmune disease therapy and vaccination efficacy.
FUNDING
This work was supported by a project grant under the joint research cooperation agreement of LMU Munich, LMU University Hospital, and Sanofi-Aventis Deutschland GmbH, as well as by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Emmy Noether Programme BA 5132/1-1 and BA 5132/1-2 (252623821), SFB 1054 Project B12 (210592381), and SFB 914 Project B03 (165054336).
Topics: Adenoids; Anti-Inflammatory Agents; B-Lymphocytes; Cells, Cultured; Child; Child, Preschool; Germinal Center; Humans; Immunophenotyping; Interleukins; Janus Kinases; Proto-Oncogene Proteins c-bcl-6; T Follicular Helper Cells; Tissue Culture Techniques; Tumor Necrosis Factor-alpha
PubMed: 32114393
DOI: 10.1016/j.ebiom.2020.102684 -
Zhongguo Zhen Jiu = Chinese Acupuncture... Feb 2020To compare the clinical effect of acupuncture at the affected side and both sides of the pharyngeal acupoints for true bulbar paralysis after cerebral infarction. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the clinical effect of acupuncture at the affected side and both sides of the pharyngeal acupoints for true bulbar paralysis after cerebral infarction.
METHODS
A total of 66 patients with true bulbar paralysis after cerebral infarction were randomly divided into an unilateral group and a bilateral group, 33 cases in each group, 1 case dropped off in each group at last. On the basis of conventional drugs and electro-nape-acupuncture treatment, the patients in the unilateral group were treated with acupuncture at the affected side's , and (Extra), while patients in the bilateral group were treated with acupuncture at the both sides' , and The treatment was performed once a day, 6 days a week, and the clinical effect was assessed after 21-day therapy. The swallowing and vocalization of the two groups were evaluated by dysphagia grading scale, Kubota water swallowing test and GRBAS grading scale before and after treatment.
RESULTS
After 21 days of treatment, the scores of the dysphagia grading scale in the two groups were both improved (<0.01), and the unilateral group was superior to the bilateral group (<0.01). The GRBAS grading scale and Kubota water swallowing test grading after treatment were improved in both groups (<0.01), and the unilateral group was superior to the bilateral group (<0.05, <0.01).
CONCLUSION
Acupuncture at the pharyngeal acupoints of the affected side achieves much better therapeutic effect on true bulbar paralysis as compared with the acupoints of the bilateral sides.
Topics: Acupuncture Points; Acupuncture Therapy; Bulbar Palsy, Progressive; Cerebral Infarction; Deglutition; Humans; Pharynx; Treatment Outcome
PubMed: 32100493
DOI: 10.13703/j.0255-2930.20190324-00044 -
FEBS Open Bio May 2020Adenoidal hypertrophy (AH) is a common disorder in the pediatric population, with common symptoms including mouth breathing, nasal congestion, hyponasal speech, snoring...
Adenoidal hypertrophy (AH) is a common disorder in the pediatric population, with common symptoms including mouth breathing, nasal congestion, hyponasal speech, snoring and obstructive sleep apnea. Although the pathogenesis of AH has not been fully elucidated, recent studies have indicated that immune responses may play an important role in AH. Tumor necrosis factor-alpha (TNF-α)-induced protein-8 like-2 (TIPE2) is a newly identified protein that negatively regulates the activation of inflammatory pathways. Here, we investigated the effect of TIPE2 in AH in children. We observed that the levels of TNF-α and interleukin-6 were greater in the adenoid tissue of AH children than in healthy control subjects (P < 0.01), and this increase was positively correlated with the severity of AH. The level of TIPE2 expression was decreased compared with control and was negatively correlated with AH. TIPE2 overexpression in primary human monocytes (isolated from adenoid tissue of children with AH) inhibited the activation of nuclear factor-κB and the expression of TNF-α and interleukin-6. These results suggest that overexpression of TIPE2 may attenuate AH through inactivation of the nuclear factor-κB signaling pathway.
Topics: Adenoids; Child; Child, Preschool; China; Female; Humans; Hypertrophy; Inflammation; Interleukin-6; Intracellular Signaling Peptides and Proteins; Male; Monocytes; RNA, Messenger; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 32100476
DOI: 10.1002/2211-5463.12821 -
European Cytokine Network Dec 2019Tonsils are important lymphoid organs in which B cells and T cells complete their maturation and identify cells that are infected by pathogens. However, the functions of...
Tonsils are important lymphoid organs in which B cells and T cells complete their maturation and identify cells that are infected by pathogens. However, the functions of T cells in human tonsils remain unclear, especially the characteristics of polyfunctional CD4 T helper cells. In this study, we used multi-color flow cytometry to analyze the expression or co-expression of effector cytokines in CD4 T cells from tonsillar tissues. We have demonstrated that tonsillar CD4 T cell can express various Th effector cytokines after short-term polyclonal stimulation, and that cytokine-producing CD4 T cells were CD45RO T cells. In addition, we analyzed the co-expression of two or more kinds of cytokines at the level of a single cell. The results showed that tonsillar CD4 T cells exhibited polyfunctionality by co-expressing two to five kinds of cytokines in the same time. These data furnished a basic theory for further understanding the differentiation of polyfunctional Th cells in human tonsils and their functions in resisting invasive microorganisms.
Topics: Adolescent; Adult; B-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Flow Cytometry; Gene Expression; Humans; Interferon-gamma; Interleukin-17; Interleukin-2; Interleukins; Ionomycin; Lymphocyte Activation; Male; Palatine Tonsil; Primary Cell Culture; Single-Cell Analysis; T-Lymphocytes, Helper-Inducer; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha; Interleukin-22
PubMed: 32096472
DOI: 10.1684/ecn.2015.0368 -
Pathology, Research and Practice Apr 2020Granular cell tumor (GCT) remains a diagnostic clinicopathologic problem because the exact frequency of its detailed morphological and clinical characteristics is...
BACKGROUND
Granular cell tumor (GCT) remains a diagnostic clinicopathologic problem because the exact frequency of its detailed morphological and clinical characteristics is unknown as most observations are collected from small series or isolated cases. Herein, our aim is to highlight the frequency of all clinicopathological characteristics of this rare tumor based in our series and the available medical (PubMed) literature.
MATERIAL AND METHODS
42 cases were evaluated for: tissue layers involved by the tumor (in skin and mucosae), growth pattern, nuclear pleomorphism, mitotic index, necrosis, spindling, calcification, hyalinization, and pustule-ovoid bodies of Milian, as well as perineural and vascular invasion, and the presence of adjacent epithelium changes, and lymphocytes and eosinophils infiltration., Follow-up was analyzed. The tumors were subclassified into benign, atypical and malignant according to Fanburg-Smith criteria and into benign or GCT of uncertain malignant potential according to Nasser criteria. The same characteristics were analyzed for 1499 cases reviewed according to PRISMA guidelines.
RESULTS
In the current series, the mean age at diagnosis was 45.8 years (range 6-69 years). Most patients were females (60 %) and the involved organs were by descending frequency: skin and subcutaneous tissue, bronchus, esophagus, breast, tongue, larynx, pharynx, gingiva, trachea, right colon, vulva, and hypopharynx. No recurrence or progression was seen, despite 32 cases were incompletely excised, with the exception of one malignant tumor. The growth pattern was either infiltrative (85.71 %) or well limited (7.14 %). Sixteen tumors had vesicular nuclei. Mitotic activity was found in two tumors. Lymphocytic infiltration was found in 14 tumors. Eosinophils were present in 6 cases. One GCT of the right colon showed extensive calcification and hyalinization. Perineural invasion was noted in 6 lesions. No vascular invasion was found. One tumor was clinically malignant and the patient died 2 years after diagnosis. Medical literature review showed similar results in terms of frequency of the reported clinical and morphological features. Among cases with available follow up, almost 20 % showed positive margins and of those 20 % developed local recurrence. According to the Fanburg-Smith criteria, 72 % would be benign, 17 % atypical and 11 % malignant tumors, while according to those of Nasser, 93 % would be benign and 7% of uncertain malignant potential. However, true malignancy, as affirmed by metastasis of GCT is found in almost 2.5 % of the cases.
CONCLUSION
GCT is a usually benign tumor, affecting any anatomic location. Necrosis and mitotic activity seem to be the most effective histologic criteria for detecting aggressive tumors, but the presence of metastasis (2.5 % of the cases) remains the most accepted definitive criterion for diagnosis of malignant GCT.
Topics: Adolescent; Adult; Aged; Child; Female; Granular Cell Tumor; Humans; Male; Middle Aged; Young Adult
PubMed: 32089415
DOI: 10.1016/j.prp.2020.152865 -
[Fistula prophylaxis with muscle-sparing, myofascial pectoralis major lobe in salvage laryngectomy].Laryngo- Rhino- Otologie Apr 2020In recurrent hypopharyngeal/laryngeal squamous cell carcinoma after radiation salvage-laryngectomy (salvage-LE) represents the best curative treatment option....
BACKGROUND
In recurrent hypopharyngeal/laryngeal squamous cell carcinoma after radiation salvage-laryngectomy (salvage-LE) represents the best curative treatment option. Pre-irradiation promotes development of pharyngocutaneous fistulas (pc-fistula). Transfer of unirradiated tissue to the surgical site reduces fistula rate. Frequently, a myocutaneous Pectoralis-major-flap (PMF) is applied. We describe a muscle sparing, myofascial PMF (ms-PMF) and its functional & aesthetic results.
METHODS
For the ms-PMF, the pectoralis major is exposed via two 8 cm long subclavicular & submammary horizontal incisions. The pectoral branch of the thoracoacromial artery, which represents the blood supply for the ms-PMF, is identified between the clavicular and sternocostal aspect of the muscle. A craniocaudal stripe of the pectoralis major is recovered and supraclaviculary transposed towards the pharynx. The clavicular and sternocostal part of the muscle remain untouched.The clear-margin resection rate (CMRR), mean overall survival (OS), complications, median length of hospital stay, & functional & aesthetic outcome were assessed.
RESULTS
In 25 patients, salvage-LE with ms-PMF was performed. The CMRR was 100 %, median OS 1.3 (follow-up 2.8) years, complications rate 16 % (4 complete lobe necroses, 3 pc-fistulas) and median inpatient stay 20 (11-78) days. Good functional outcome were observed: limitations of oral food intake occurred in 2-, limitations in voice rehabilitation in 3 patients. Wound healing disorders without lobe necrosis were not observed. The aesthetic results were appealing.
CONCLUSION
The ms-PMF is a less invasive & safe procedure for fistula prophylaxis in salvage-LE with favorable functional & aesthetic results.
Topics: Cutaneous Fistula; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Laryngectomy; Pectoralis Muscles; Pharyngeal Diseases; Retrospective Studies; Salvage Therapy
PubMed: 32079025
DOI: 10.1055/a-1099-9688