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  1. Top of page
  2. Cover image
  3. To bug or not to bug — treatment with ‘dirty’ pollen extract may reinforce an established allergic response
  4. Class switch recombination requires an intact MyD88-binding site for TACI
  5. Promiscuous B cells may confer enduring memory of conserved Flu epitopes
  6. Tc9 cells reveal the complex functional heterogeneity of CD8+ T cells
  7. The burden of chronic stress: Corticosterone as a double-edged sword
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The cover features a digitally-coloured histology image of a renal glomerulus from an IgG Fc receptor IIB (FcγRIIB)-deficient C57BL/6 (KO1) mouse. The original periodic acid-Schiff/hematoxylin-stained section showed that KO1 mice have normal glomerular histology despite the development of rheumatoid arthritis (RA). The image is taken from the article by Kawano et al. (pp. 770–778) in which it is shown that the introduction of a Y chromosome-linked autoimmune acceleration (Yaa) mutation in the KO1 strain (KO1.Yaa) leads to the development of systemic lupus erythematosus (SLE) rather than RA. Kawano et al. suggest that their model clarifies the shared and disease-specific mechanisms underlying the clinically distinct autoimmune diseases RA and SLE. The added colour is purely for aesthetic purposes and has no biological relevance.

To bug or not to bug — treatment with ‘dirty’ pollen extract may reinforce an established allergic response

  1. Top of page
  2. Cover image
  3. To bug or not to bug — treatment with ‘dirty’ pollen extract may reinforce an established allergic response
  4. Class switch recombination requires an intact MyD88-binding site for TACI
  5. Promiscuous B cells may confer enduring memory of conserved Flu epitopes
  6. Tc9 cells reveal the complex functional heterogeneity of CD8+ T cells
  7. The burden of chronic stress: Corticosterone as a double-edged sword
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Specific allergen immunotherapy, the only curative treatment for allergy, involves repeated doses of allergen extracts to achieve de-sensitisation and tolerance. Varying levels of microbial extract contamination may modulate immune responses — but whether such contamination is beneficial or detrimental to clinical efficacy has not been clarified to date. In this issue, Mittag et al. demonstrate that ryegrass pollen-associated PAMPs, such as LPS, enhance the pre-established Th2-bias in peripheral blood samples from allergic subjects. Exposure of human peripheral blood to LPS elicited increased inflammatory cytokine secretion, including Th2 cytokines, and increased Th2-cell induction with impaired Foxp3hi Treg-cell induction. Minor differences were observed in IL-10-secreting T-cell induction with negligible IL-17 secretion. Similar observations were made in non-atopic subjects but with a reduction in the Th2 response. These data provide important insight into adjuvant properties of pollen microbial contaminants and suggest that adjuvants for allergen-specific immunotherapy should enhance Treg cells rather than target immune deviation from Th2 to Th1.

Class switch recombination requires an intact MyD88-binding site for TACI

  1. Top of page
  2. Cover image
  3. To bug or not to bug — treatment with ‘dirty’ pollen extract may reinforce an established allergic response
  4. Class switch recombination requires an intact MyD88-binding site for TACI
  5. Promiscuous B cells may confer enduring memory of conserved Flu epitopes
  6. Tc9 cells reveal the complex functional heterogeneity of CD8+ T cells
  7. The burden of chronic stress: Corticosterone as a double-edged sword

CD40 engagement initiates T-dependent class-switch recombination (CSR), whereas dual TLR–TACI engagement not only induces T-independent CSR, but also plays a role in the early stages of T-dependent antibody responses. CSR induction by TLR9 and TACI involves the translocation of NF-κB to the nucleus via MyD88 dimerization. A TACI highly-conserved cyto­plasmic domain (THC) has been implicated in MyD88 recruitment, and a missense mutation predicted to affect the THC has been previously identified in a pediatric patient with hypogammaglobulinemia. In this issue, Almejun et al. show that B cells from this unique patient have attenuated TACI signaling with a failure to integrate signals from TACI and TLR9, or TACI and CD40, to achieve optimal antibody production. The authors also demonstrate that the mutation affecting the MyD88 binding site prevents the association of MyD88 with TACI in a specific manner. Collectively, these results highlight the requirement for an intact MyD88-binding site in TACI to trigger CSR.

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Promiscuous B cells may confer enduring memory of conserved Flu epitopes

  1. Top of page
  2. Cover image
  3. To bug or not to bug — treatment with ‘dirty’ pollen extract may reinforce an established allergic response
  4. Class switch recombination requires an intact MyD88-binding site for TACI
  5. Promiscuous B cells may confer enduring memory of conserved Flu epitopes
  6. Tc9 cells reveal the complex functional heterogeneity of CD8+ T cells
  7. The burden of chronic stress: Corticosterone as a double-edged sword
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Influenza viruses continuously “change faces” to evade human immune defenses. For this reason, influenza vaccines must be reformulated almost yearly. We are starting to identify traits that remain constant in all influenza viruses, although how frequently these traits are seen by the immune system, and if they remain imprinted in immune memory, is not currently known. In this issue, Buricchi et al. show that about half of human adults have measurable numbers of memory B cells recognizing traits shared between viruses responsible for past seasonal epidemics and avian influenza viruses, which never circulated in humans. In addition, the authors observe that subjects with high numbers of these memory B cells mount accelerated responses to vaccination against the novel avian influenza virus. These data strongly support research and development programs aimed at designing novel vaccines capable of promoting the preferential priming of memory B cells reactive to antigenic traits conserved in all influenza viruses.

Tc9 cells reveal the complex functional heterogeneity of CD8+ T cells

  1. Top of page
  2. Cover image
  3. To bug or not to bug — treatment with ‘dirty’ pollen extract may reinforce an established allergic response
  4. Class switch recombination requires an intact MyD88-binding site for TACI
  5. Promiscuous B cells may confer enduring memory of conserved Flu epitopes
  6. Tc9 cells reveal the complex functional heterogeneity of CD8+ T cells
  7. The burden of chronic stress: Corticosterone as a double-edged sword

CD4+ T helper cells have been shown to differentiate into various subsets after antigen recognition. In addition to well-known Th1 and Th2 cells, new subpopulations such as Th17, Tfh and Th9 cells have been identified. In contrast, CD8+ T cells were considered to exhibit mainly cytotoxic function. The development of the cytotoxic CD8+ T-cell subpopulation is mainly determined by expression of the transcription factors Eomesodermin and T-bet. In this issue, Visekruna et al. describe a new CD8+ T-cell subpopulation in humans and mice termed Tc9 cells, which produce IL-9, display low cytotoxicity and contribute to Th2-mediated airway inflammation. Similarly to Th9 cells, Tc9 cells differentiate when cultured with TGF-β and IL-4 and require the transcription factors IRF4 and STAT6, indicating common molecular pathways. Recently, the authors described mildly cytotoxic Tc17 cells which are likewise IRF4-dependent and support autoimmune encephalomyelitis. These novel data point to the developmental similarities between CD4+ and CD8+ T cells.

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The burden of chronic stress: Corticosterone as a double-edged sword

  1. Top of page
  2. Cover image
  3. To bug or not to bug — treatment with ‘dirty’ pollen extract may reinforce an established allergic response
  4. Class switch recombination requires an intact MyD88-binding site for TACI
  5. Promiscuous B cells may confer enduring memory of conserved Flu epitopes
  6. Tc9 cells reveal the complex functional heterogeneity of CD8+ T cells
  7. The burden of chronic stress: Corticosterone as a double-edged sword
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Stress suppresses the immune system, shifting it towards anti-inflammatory responses through the secretion of steroids such as corticosterone (CORT). Paradoxically, chronic exposure to stress is also associated with increased susceptibility to autoimmune diseases characterized by inflammatory responses. In this issue, Harpaz et al. show that exposing mice to chronic stress increases systemic CORT levels, which lead to immune cell loss and a decreased ratio of regulatory T cells among the CD4+ lymphocytes. Moreover, the authors demonstrate that the surviving lymphocytes are resistant to steroid signaling manifested by increased pro-inflammatory cytokine responses in the presence of steroids. Upon the induction of EAE — a model of multiple sclerosis associated with acute inflammation and massive CORT release — in mice, lymphocytes from stressed mice exhibited increased pro-inflammatory cytokine production which then increased the susceptibility of stressed mice to EAE. These findings suggest that a stressful environment may have maladaptive consequences on CORT-induced immune regulation, leading to pathogenic autoimmunity.