ResearchPad - 319 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Interstitial-resident memory CD8<sup>+</sup> T cells sustain frontline epithelial memory in the lung]]> https://www.researchpad.co/article/elastic_article_15299

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<![CDATA[CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways]]> https://www.researchpad.co/article/elastic_article_15296 Resident memory T cells (TRM cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung TRM cell populations to protective immunity and the factors that govern their localization to different compartments of the lung are not well understood. Here, we show that airway and interstitial TRM cells have distinct effector functions and that CXCR6 controls the partitioning of TRM cells within the lung by recruiting CD8 TRM cells to the airways. The absence of CXCR6 significantly decreases airway CD8 TRM cells due to altered trafficking of CXCR6−/− cells within the lung, and not decreased survival in the airways. CXCL16, the ligand for CXCR6, is localized primarily at the respiratory epithelium, and mice lacking CXCL16 also had decreased CD8 TRM cells in the airways. Finally, blocking CXCL16 inhibited the steady-state maintenance of airway TRM cells. Thus, the CXCR6/CXCL16 signaling axis controls the localization of TRM cells to different compartments of the lung and maintains airway TRM cells.

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<![CDATA[Modulation of the fungal mycobiome is regulated by the chitin-binding receptor FIBCD1]]> https://www.researchpad.co/article/elastic_article_15294 Host–microbiota interactions are critical in regulating mammalian health and disease. In addition to bacteria, parasites, and viruses, beneficial communities of fungi (the mycobiome) are important modulators of immune- and tissue-homeostasis. Chitin is a major component of the fungal cell wall, and fibrinogen C containing domain 1 (FIBCD1) is a chitin-binding protein; however, the role of this molecule in influencing host–mycobiome interactions in vivo has never been examined. Here, we identify direct binding of FIBCD1 to intestinal-derived fungi and demonstrate that epithelial-specific expression of FIBCD1 results in significantly reduced fungal colonization and amelioration of fungal-driven intestinal inflammation. Collectively, these results identify FIBCD1 as a previously unrecognized microbial pattern recognition receptor through which intestinal epithelial cells can recognize and control fungal colonization, limit fungal dysbiosis, and dampen intestinal inflammation.

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<![CDATA[A CCL1/CCR8-dependent feed-forward mechanism drives ILC2 functions in type 2–mediated inflammation]]> https://www.researchpad.co/article/elastic_article_15292 Group 2 innate lymphoid cells (ILC2s) possess indispensable roles during type 2–mediated inflammatory diseases. Although their physiological and detrimental immune functions seem to depend on the anatomical compartment they reside, their tissue tropism and the molecular and immunological processes regulating the self-renewal of the local pool of ILC2s in the context of inflammation or infection are incompletely understood. Here, we analyzed the role of the CC-chemokine receptor CCR8 for the biological functions of ILC2s. In vitro and in vivo experiments indicated that CCR8 is in comparison to the related molecule CCR4 less important for migration of these cells. However, we found that activated mouse and human ILC2s produce the CCR8 ligand CCL1 and are a major source of CCL1 in vivo. CCL1 signaling to ILC2s regulates their proliferation and supports their capacity to protect against helminthic infections. In summary, we identify a novel chemokine receptor–dependent mechanism by which ILC2s are regulated during type 2 responses.

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<![CDATA[Loss of IL-10 signaling in macrophages limits bacterial killing driven by prostaglandin E2]]> https://www.researchpad.co/article/N47ae0984-aed2-400d-b024-8d4692148a59

Cytokines and lipid mediators are key regulators of inflammation; but how they are mechanistically linked is poorly understood. Here, Mukhopadhyay et al. show a novel regulation between cytokine IL-10 and lipid mediator PGE2 that functionally connects them to intestinal inflammation.

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<![CDATA[Effects of natalizumab therapy on intrathecal antiviral antibody responses in MS]]> https://www.researchpad.co/article/N532ddc91-abf8-47f6-87f3-20866d3c3b08

Objective

To investigate the effects of natalizumab (NAT) treatment on intrathecally produced antiviral antibodies in MS.

Methods

We performed a longitudinal, observational study analyzing both serum and CSF samples collected before and during NAT treatment for antibodies against measles, rubella, mumps, influenza, entero, herpes, and polyoma viruses, including JC polyomavirus (JCV) and its nearest homologue BK polyomavirus (BKV), and bacterial control antigens by ELISA to determine the antigen-specific CSF antibody index (CAI). CAI ≥1.5 indicated intrathecal synthesis of antigen-specific antibodies. Oligoclonal bands (OCBs) by isoelectric focusing and total IgG, IgM, and IgA by immunonephelometry were analyzed additionally.

Results

Intrathecal synthesis of JCV- and BKV-specific IgG was detected in 20% of patients with MS at baseline and was lost significantly more frequently during NAT treatment compared with other intrathecal antiviral and antibacterial antibody reactivities. Peripheral JCV- and BKV-specific antibody responses persisted, and no cross-reactivity between JCV- and BKV-specific CSF antibodies was found. Intrathecal production of antibodies against measles, rubella, and zoster antigens (MRZ reaction) was most prevalent and persisted (73.3% before vs 66.7% after 1 year of NAT therapy). CSF OCBs also persisted (93.3% vs 80.0%), but total CSF IgG and IgM levels declined significantly.

Conclusions

These data indicate that JCV-specific antibodies are produced intrathecally in a minority of patients with MS, and NAT treatment affects the intrathecal humoral immune response against JCV relatively specifically compared with other neurotropic viruses. Further studies are needed to determine whether this effect translates to higher risk of progressive multifocal leukoencephalopathy development.

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<![CDATA[LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma]]> https://www.researchpad.co/article/5c91078bd5eed0c4841a44b2

This study provides strong evidence that intestinal commensal LPS desensitizes lung epithelial cells and therefore diminishes allergic responses to inhaled allergens. A host lipase, acyloxyacyl hydrolase (AOAH), prevents the desensitization by inactivating commensal LPS.

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<![CDATA[Eosinophils can more than kill]]> https://www.researchpad.co/article/5c69ecbcd5eed0c48414e2b9

In this issue of JEM, Arnold et al. demonstrate that eosinophils suppress mucosal inflammation by directly interacting with pro-inflammatory Th1 cells. This emphasizes the dual role of eosinophils, which can act both as effector cells that control an infection and as immunomodulatory cells that promote immune homeostasis.

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<![CDATA[Effector CD4 T cells with progenitor potential mediate chronic intestinal inflammation]]> https://www.researchpad.co/article/5c368393d5eed0c4841f42b9

Effector CD4 T cells with progenitor properties are present during chronic intestinal inflammation, and these cells support the maintenance of disease. The expression of the glycosyltransferase ST6Gal-I by these cells promotes cell survival and TCF1 levels.

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<![CDATA[A20 and ABIN-1 team up against intestinal epithelial cell death]]> https://www.researchpad.co/article/5c368386d5eed0c4841f4084

A20 and its binding partner ABIN-1 are genetically linked to inflammatory diseases. In this issue of JEM, Kattah et al. demonstrate that simultaneous deletion in a mouse model leads to instantaneous cell death in the intestinal epithelium and mortality.

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<![CDATA[Autophagy protein ATG16L1 prevents necroptosis in the intestinal epithelium]]> https://www.researchpad.co/article/5c01f8dbd5eed0c4842befb3

Matsuzawa-Ishimoto et al. show that autophagy gene ATG16L1, which is associated with inflammatory diseases of the gastrointestinal tract, is essential for preventing necroptotic cell death and loss of Paneth cells in the intestinal epithelium.

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<![CDATA[R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease]]> https://www.researchpad.co/article/5c01f8d2d5eed0c4842bedad

Hayase et al. show that R-Spondin1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of α-defensins. Administration of R-Spondin1 or recombinant α-defensin prevents dysbiosis mediated by graft-versus-host disease, representing a novel approach to restore intestinal ecosystems and homeostasis.

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