Current Print IssueJournal of Experimental Medicine RSS feed -- current issueRegulation of the germinal center gene program by interferon (IFN) regulatory factor 8IFN consensus sequence-binding protein- June 9, 2008http://www.jem.org/cgi/content/short/205/6/1507?rss=1 A unique B2 B cell subset in the intestine- June 9, 2008 Over 80% of the body's activated B cells are located in mucosal sites, including the intestine. The intestine contains IgM+ B cells, but these cells have not been characterized phenotypically or in terms of their developmental origins. We describe a previously unidentified and unique subset of immunoglobulin M+ B cells that present with an AA4.1–CD21–CD23– major histocompatibility complex class IIbright surface phenotype and are characterized by a low frequency of somatic...http://www.jem.org/cgi/content/short/205/6/1343?rss=1 "Re-educating" tumor-associated macrophages by targeting NF-kappaB- June 9, 2008 The nuclear factor B (NF-B) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-B in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive "alternative" phenotype that requires IB kinase β–mediated NF-B activation. When NF-B signaling is inhibited specifically in TAMs, they...http://www.jem.org/cgi/content/short/205/6/1261?rss=1 Development and characterization of IL-21-producing CD4+ T cells- June 9, 2008 It has recently been shown that interleukin (IL)-21 is produced by Th17 cells, functions as an autocrine growth factor for Th17 cells, and plays critical roles in autoimmune diseases. In this study, we investigated the differentiation and characteristics of IL-21–producing CD4+ T cells by intracellular staining. Unexpectedly, we found that under Th17-polarizing conditions, the majority of IL-21–producing CD4+ T cells did not produce IL-17A and -17F. We also found that IL-6 and -21...http://www.jem.org/cgi/content/short/205/6/1369?rss=1 An antiinflammatory role for IKKbeta through the inhibition of "classical" macrophage activation- June 9, 2008 The nuclear factor B (NF-B) pathway plays a central role in inflammation and immunity. In response to proinflammatory cytokines and pathogen-associated molecular patterns, NF-B activation is controlled by IB kinase (IKK)β. Using Crelox-mediated gene targeting of IKKβ, we have uncovered a tissue-specific role for IKKβ during infection with group B streptococcus. Although deletion of IKKβ in airway epithelial cells had the predicted effect of inhibiting inflammation and...http://www.jem.org/cgi/content/short/205/6/1269?rss=1 Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7- June 9, 2008 Ubiquitination is a posttranslational mechanism that controls diverse cellular processes. We focus here on the ubiquitin ligase Fbw7, a recently identified hematopoietic tumor suppressor that can target for degradation several important oncogenes, including Notch1, c-Myc, and cyclin E. We have generated conditional Fbw7 knockout animals and inactivated the gene in hematopoietic stem cells (HSCs), progenitors, and their differentiated progeny. Deletion of Fbw7 specifically and rapidly affects...http://www.jem.org/cgi/content/short/205/6/1395?rss=1 Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis- June 9, 2008 The high rate of mortality in patients with sepsis results from an inappropriately amplified systemic inflammatory response to infection. Toll-like receptors (TLRs) are important for the activation of innate immunity against microbial pathogens. We demonstrate a critical role of TLR9 in the dysregulated immune response and death associated with sepsis. Compared with wild-type (WT) mice, TLR9–– mice exhibited lower serum inflammatory cytokine levels, higher bacterial clearance, and...http://www.jem.org/cgi/content/short/205/6/1277?rss=1 A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies- June 9, 2008 The presence of serum bactericidal antibodies is a proven correlate of protection against systemic infection with the important human pathogen Neisseria meningitidis. We have identified three serogroup C N. meningitidis (MenC) isolates recovered from patients with invasive meningococcal disease that resist killing by bactericidal antibodies induced by the MenC conjugate vaccine. None of the patients had received the vaccine, which has been successfully introduced in countries in North America...http://www.jem.org/cgi/content/short/205/6/1423?rss=1 Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma- June 9, 2008 Eosinophils have been implicated as playing a major role in allergic airway responses. However, the importance of these cells to the development of this disease has remained ambiguous despite many studies, partly because of lack of appropriate model systems. In this study, using transgenic murine models, we more clearly delineate a role for eosinophils in asthma. We report that, in contrast to results obtained on a BALBc background, eosinophil-deficient C57BL6 dblGATA mice (eosinophil-null mice.http://www.jem.org/cgi/content/short/205/6/1285?rss=1 Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells- June 9, 2008 We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the human dectin-1 ligand β-glucan alone or in combination with TLR2 ligands, mimicking induction by zymosan. TLR2...http://www.jem.org/cgi/content/short/205/6/1447?rss=1 |