Explore the vast range of titles available.

TSLP's role in allergy The cytokine thymic stromal lymphopoietin (TSLP) has been described as the master switch of allergic inflammation. Here, TSLP is shown to induce the development of basophils from bone-marrow progenitors and to activate peripheral basophils in an interleukin-3 (IL-3)-independent manner. Basophils elicited by TSLP differ from those dependent on IL-3 both phenotypically and functionally, and may play an important part in allergic diseases associated with T-helper type 2 cells. CD4 + T-helper type 2 (T H 2) cells, characterized by their expression of interleukin (IL)-4, IL-5, IL-9 and IL-13, are required for immunity to helminth parasites 1 and promote the pathological inflammation associated with asthma and allergic diseases 2 . Polymorphisms in the gene encoding the cytokine thymic stromal lymphopoietin (TSLP) are associated with the development of multiple allergic disorders in humans, indicating that TSLP is a critical regulator of T H 2 cytokine-associated inflammatory diseases 3 , 4 , 5 , 6 . In support of genetic analyses, exaggerated TSLP production is associated with asthma, atopic dermatitis and food allergies in patients, and studies in murine systems demonstrated that TSLP promotes T H 2 cytokine-mediated immunity and inflammation 5 , 7 , 8 , 9 , 10 , 11 , 12 . However, the mechanisms through which TSLP induces T H 2 cytokine responses remain poorly defined. Here we demonstrate that TSLP promotes systemic basophilia, that disruption of TSLP–TSLPR interactions results in defective basophil responses, and that TSLPR-sufficient basophils can restore T H 2-cell-dependent immunity in vivo . TSLP acted directly on bone-marrow-resident progenitors to promote basophil responses selectively. Critically, TSLP could elicit basophil responses in both IL-3–IL-3R-sufficient and -deficient environments, and genome-wide transcriptional profiling and functional analyses identified heterogeneity between TSLP-elicited versus IL-3-elicited basophils. Furthermore, activated human basophils expressed TSLPR, and basophils isolated from eosinophilic oesophagitis patients were distinct from classical basophils. Collectively, these studies identify previously unrecognized heterogeneity within the basophil cell lineage and indicate that expression of TSLP may influence susceptibility to multiple allergic diseases by regulating basophil haematopoiesis and eliciting a population of functionally distinct basophils that promote T H 2 cytokine-mediated inflammation.

Cytokine-producing innate lymphoid cells are found at mucosal surfaces. Artis and Wherry and their colleagues show that innate 'nuocyte-like' cells accumulate in virus-infected lungs and contribute to the repair of tissues. Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor α-chain (CD25), IL-7 receptor α-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.

The roles of individual microRNAs in the CD8 + T cell response remain mostly unexplored. Katsikis and colleagues show that miR-155 regulates type I interferon responsiveness and CD8 + T cell responses to pathogens in vivo . We found upregulation of expression of the microRNA miR-155 in primary effector and effector memory CD8 + T cells, but low miR-155 expression in naive and central memory cells. Antiviral CD8 + T cell responses and viral clearance were impaired in miR-155-deficient mice, and this defect was intrinsic to CD8 + T cells, as miR-155-deficient CD8 + T cells mounted greatly diminished primary and memory responses. Conversely, miR-155 overexpression augmented antiviral CD8 + T cell responses in vivo . Gene-expression profiling showed that miR-155-deficient CD8 + T cells had enhanced type I interferon signaling and were more susceptible to interferon's antiproliferative effect. Inhibition of the type I interferon–associated transcription factors STAT1 or IRF7 resulted in enhanced responses of miR-155-deficient CD8 + T cells in vivo . We have thus identified a previously unknown role for miR-155 in regulating responsiveness to interferon and CD8 + T cell responses to pathogens in vivo .

Critical values denote laboratory test results indicating a life-threatening situation. The outcomes of this premise have not been rigorously evaluated. Five years of inpatient admissions were examined for critical or \"near-critical\" results (total admissions = 165,066; total test results = 872,503). In-hospital mortality was examined as a function of time and degree of test result abnormality. Some critical value thresholds appropriately identified patients at risk for death (eg, elevated potassium). Other thresholds were too conservative (elevated hematocrit, hemoglobin) or not conservative enough (elevated lactate). Mortality risk for most critical values was time dependent, but some critical values showed no temporal effect on mortality (elevated activated partial thromboplastin time [APTT], international normalized ratio [INR], and glucose). Following an initial critical result, further worsening was associated with increased mortality. Prior hospital admission within 30 days was a predictor of lower mortality for some (elevated APTT, INR, potassium, and sodium; low glucose, hematocrit, hemoglobin, and potassium) but not other critical values (elevated lactate, glucose, hematocrit, and hemoglobin; low sodium). Only a subset of laboratory critical value thresholds was optimally chosen for increased risk of in-hospital mortality, with a time urgency for most but not all critical values. For many tests, a prior hospital admission imparted a decreased risk of in-hospital death.

We found upregulation of expression of the microRNA miR-155 in primary effector and effector memory [CD8.sup.+] T cells, but low miR-155 expression in naive and central memory cells. Antiviral [CD8.sup.+] T cell responses and viral clearance were impaired in miR-155-deficient mice, and this defect was intrinsic to [CD8.sup.+] T cells, as miR-155-deficient [CD8.sup.+] T cells mounted greatly diminished primary and memory responses. Conversely, miR-155 overexpression augmented antiviral [CD8.sup.+] T cell responses in vivo. Gene-expression profiling showed that miR-155-deficient [CD8.sup.+] T cells had enhanced type I interferon signaling and were more susceptible to interferon's antiproliferative effect. Inhibition of the type I interferon-associated transcription factors STAT1 or IRF7 resulted in enhanced responses of miR-155-deficient [CD8.sup.+] T cells in vivo. We have thus identified a previously unknown role for miR-155 in regulating responsiveness to interferon and [CD8.sup.+] T cell responses to pathogens in vivo.

Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor a-chain (CD25), IL-7 receptor a-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.