SEARCH

SEARCH BY CITATION

Cover image

  1. Top of page
  2. Cover image
  3. Fatty acids against cancer
  4. FCRL3 counter-regulates TLR9-mediated B-cell activation
  5. Multi-tasking CD8+ T cells calm immune activation in HIV-1 infection
  6. NIP and tuck – the plastic circuitry of pDCs
  7. Intrathymic Notch signaling controls fetal αβ and γδ T-cell development
image

The cover features a photograph of two neonatal nurse sharks. The image background shows two consecutive, pseudocolored, in situ hybridization-stained sections from nurse shark spleen tissue. The tissue section image is taken from the article by Castro et al. (pp. 3061–3075) in which the authors describe antibody-secreting cells in neonatal, juvenile, and adult nurse sharks, which do not express the “master regulator” transcription factor of plasma cells, Blimp-1. Although Blimp-1 was expressed in adult cells expressing monomeric IgM (7S), all Ig-secreting cells in neonatal sharks were Blimp-1-negative, and Blimp-1 was rarely detected in adult J-chain-positive, pentameric (19S) IgM-secreting cells. These findings suggest that Blimp-1 is not required to maintain memory B cells in the shark spleen but is required for terminating the B-cell program following adaptive immunity.

Fatty acids against cancer

  1. Top of page
  2. Cover image
  3. Fatty acids against cancer
  4. FCRL3 counter-regulates TLR9-mediated B-cell activation
  5. Multi-tasking CD8+ T cells calm immune activation in HIV-1 infection
  6. NIP and tuck – the plastic circuitry of pDCs
  7. Intrathymic Notch signaling controls fetal αβ and γδ T-cell development

10.1002/eji.201343472, pp 2943–2965

image

Polyunsaturated fatty acids (PUFAs) have long been shown to have immunosuppressive effects, the mechanism(s) of which remains to be elucidated. In this issue, Yan et al. show that PUFA enhances the accumulation and the function of mouse bone marrow-derived myeloid-derived suppressor cells (MDSCs), a negative immune regulator cell type. Administration of PUFAs causes significant activation of the JAK-STAT3 pathway, which leads to the induction of S100A8/A9 and the NADPH oxidase subunit p47phox, which are important genes for MDSC expansion and activation respectively. The enhanced generation of MDSCs by exposure to PUFA could dampen T-cell responses under tumor-bearing conditions and facilitate tumor immune escape. These findings demonstrate that MDSCs mediate the suppressive effects of PUFAs on the immune system.

FCRL3 counter-regulates TLR9-mediated B-cell activation

  1. Top of page
  2. Cover image
  3. Fatty acids against cancer
  4. FCRL3 counter-regulates TLR9-mediated B-cell activation
  5. Multi-tasking CD8+ T cells calm immune activation in HIV-1 infection
  6. NIP and tuck – the plastic circuitry of pDCs
  7. Intrathymic Notch signaling controls fetal αβ and γδ T-cell development

10.1002/eji.201243068, pp 2980–2992

image

Members of the extended Fc receptor-like (FCRL) family are preferentially expressed by B cells, possess complex tyrosine-based immunoregulatory properties, and are linked with a growing number of immune-mediated disorders. Although most have cytoplasmic immunoreceptor tyrosine-based activation (ITAM) and inhibitory motifs (ITIM), FCRLs have generally been found to inhibit B-cell receptor signaling. However, the role of FCRLs in innate responses and potential for positive regulation therein are largely unexplored. In this issue, Li et al. demonstrate that the disease-associated FCRL3 molecule can enhance TLR9 signaling, but has counter-regulatory effects on human B-cell differentiation and proliferation. The TLR9 agonist CpG drives B-cell activation, proliferation, survival, and plasma cell differentiation. While concomitant FCRL3 ligation, as well as NF-κB and MAPK p38 and ERK pathway stimulation, augment these outcomes, FCRL3 ligation represses the generation of antibody-secreting cells by halting BLIMP1 production in an ERK-dependent manner. These results reveal novel regulatory properties for the FCRLs in innate signaling.

Multi-tasking CD8+ T cells calm immune activation in HIV-1 infection

  1. Top of page
  2. Cover image
  3. Fatty acids against cancer
  4. FCRL3 counter-regulates TLR9-mediated B-cell activation
  5. Multi-tasking CD8+ T cells calm immune activation in HIV-1 infection
  6. NIP and tuck – the plastic circuitry of pDCs
  7. Intrathymic Notch signaling controls fetal αβ and γδ T-cell development

10.1002/eji.201343646, pp 2875–2885

image

Interleukin-10 (IL-10) can limit potentially harmful proinflammatory responses but may also interfere with pathogen clearance. It is elevated in the blood throughout HIV-1 infection, but it is unclear whether this is a viral evasion mechanism or an appropriate response to immune activation. In this issue, Clutton et al. identify a subset of CD8+ T cells as the predominant HIV-specific producers of IL-10 in the peripheral blood of individuals with chronic untreated HIV-1 infection. These cells lacked a conventional regulatory T-cell phenotype and, unexpectedly, a high proportion co-produce IFN-γ. The authors use a novel system to selectively deplete HIV-specific IL-10+ CD8+ T cells from culture and observe that this leads to increased activation of other CD8+ T cells and monocytes. These induced monocytes also upregulate IL-6 when stimulated with HIV-1 gag proteins. This study identifies, for the first time, a role for HIV-specific IL-10+ CD8+ T cells in limiting immune activation during chronic HIV infection.

NIP and tuck – the plastic circuitry of pDCs

  1. Top of page
  2. Cover image
  3. Fatty acids against cancer
  4. FCRL3 counter-regulates TLR9-mediated B-cell activation
  5. Multi-tasking CD8+ T cells calm immune activation in HIV-1 infection
  6. NIP and tuck – the plastic circuitry of pDCs
  7. Intrathymic Notch signaling controls fetal αβ and γδ T-cell development

10.1002/eji.201343498, pp 2993–3005

image

Current thinking suggests that plasmacytoid dendritic cells (pDCs) link innate and adaptive immunity by sequential production of type I interferon (IFN-I) and T-cell stimulation. The discovery of pDC subsets with individual functions, however, indicates that the aforementioned model could instead reflect a functional dichotomy of the pDC pool.

In this issue, Niederquell et al. describe two developmental stages of pDCs in mice, characterized by differential expression of the Sca-1 receptor. Sca-1 pDCs appear early in development and produce IFN-I upon TLR9 triggering in an osteopontin (Opn-i)-dependent manner. Based on this property Sca-1 pDCs represent the true “natural IFN-producing” cells (NIPs). In response to endogenous IFN-I, Sca-1 pDCs upregulate Sca-1 and downregulate Opn-i, which in turn leads to the dysfunction of the TLR9-dependent transcription of IFN-I and loss of NIP function. These data give a new insight into the stepwise acquisition of pDC effector functions during development and their regulation by environmental factors.

Intrathymic Notch signaling controls fetal αβ and γδ T-cell development

  1. Top of page
  2. Cover image
  3. Fatty acids against cancer
  4. FCRL3 counter-regulates TLR9-mediated B-cell activation
  5. Multi-tasking CD8+ T cells calm immune activation in HIV-1 infection
  6. NIP and tuck – the plastic circuitry of pDCs
  7. Intrathymic Notch signaling controls fetal αβ and γδ T-cell development

10.1002/eji.201343527, pp 2845–2853

image

Notch signaling plays an essential role for T-cell specification in the adult thymus. However little is known about the role of Notch during fetal T-cell development, which exhibits unique features compared with that in the adult. In this issue, Ferrero et al. demonstrate that ablation of the Notch ligand Delta-Like 4 (DL4) specifically in fetal thymus epithelium blocks the development of both αβ and γδ T-cell lineages in mice. Interestingly the fetal thymus harbors unique populations of γδ T cells expressing invariant TCRs, including a Vγ3/Vδ1 subset that differentiates into dendritic epidermal T cells (DETCs) regulating immune surveillance and homeostasis in the skin. In the absence of DL4 on epithelial cells Vγ3/Vδ1 thymocyte development is severely impaired and DETC numbers in the skin are consequently reduced. These data reveal a common requirement for DL4-mediated Notch signaling during embryonic and adult thymopoiesis, despite the special features of the fetal thymus microenvironment.