Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by the production of pathogenic autoantibodies. A new study demonstrates that passive antibody specific for the TNF family member, CD154, ameliorates disease by reducing levels of self-reactive antibody in the serum. This study demonstrates a substantial potential for anti-CD154 antibody in the treatment of humoral autoimmunity.
Garnett Kelsoe
Ever more unexpected roles for the LDL receptor gene family in a variety of cellular signaling pathways continue to emerge. Three recent studies now add another function to this collection. By interacting with active tissue-type plasminogen activator, LDL receptor–related protein appears to control permeability of the blood-brain barrier, vascular tone, and the expression of MMPs. All of these parameters impact upon postischemic infarct size following stroke. These novel findings are discussed in the context of known mechanisms of signaling by the LDL receptor family.
Joachim Herz
Mice haploinsufficient for elastin develop structural changes in vessel walls similar to those seen in patients with mutations in the elastin gene. A new study demonstrates that due to mechanical changes in the vessel wall, these animals exhibit increased mean arterial pressures. The results evoke the possibility that alterations in elastin may contribute to the development of essential hypertension in patients.
Jeanine D’Armiento
Naturally arising CD4+ regulatory T cells, which engage in the maintenance of immunologic self-tolerance, specifically express FOXP3, which encodes a transcription-repressor protein. Genetic defects in FOXP3 cause IPEX, an X-linked autoimmune/inflammatory syndrome. With FOXP3 as a specific marker for regulatory CD4+ T cells in humans, it is now possible to determine their origin and developmental pathway .
Shimon Sakaguchi
Intestinal colonic crypts are derived from a stem cell population located at the base of each crypt. A new analysis of mitochondrial function and of the rates of mitochondrial DNA (mtDNA) mutation in individual crypts shows that mtDNA mutations arise in stem cells — and at a surprisingly high frequency. Because crypts turn over extremely rapidly (about once per week), somatic mtDNA mutations can “take over the system” and even become homoplasmic, in a manner similar to what has been shown to occur in tumors.
Eric A. Schon
Antigen-specific lymphocytes are involved in synovial proliferation within inflamed joints. Activated lymphocytes and synoviocytes from patients with rheumatoid arthritis express receptors that can bind TNF-related apoptosis-inducing ligand (TRAIL). A new study demonstrates that DCs pulsed with collagen and transduced with an adenovirus-based vector able to express TRAIL limit the incidence of arthritis in a model of collagen-induced arthritis and joint inflammation. These results suggest that gene-modified cell therapy represents a therapeutic option for systemic rheumatic diseases.
George C. Tsokos, Maria Tsokos
Paracrine signaling via platelet-derived growth factor B (PDGFB), expressed by endothelial cells, and its receptor PDGFR-β, expressed by pericytes, plays a central role in blood vessel maturation. A new study reveals that it is not just the presence of PDGFB, but how it is presented to pericytes, that determines the quality of the endothelium-pericyte interaction.
Rakesh K. Jain, Michael F. Booth
Toll-like receptors (TLRs) recognize microbial molecular signatures and can initiate innate immune responses against invading pathogens. A new study reports how TLR2 expression by endothelia is locally upregulated by the action of activated polymorphonuclear neutrophils via an unprecedented mechanism involving cell-cell interaction and NAD(P)H oxidase. The report reveals yet another way in which the primordial innate immune system is remarkably complex.
Eicke Latz, Douglas T. Golenbock
Uroguanylin is a peptide hormone that regulates sodium excretion by the kidney when excess NaCl is consumed. A new study demonstrates that mice deficient in uroguanylin have blunted urinary sodium excretion responses to oral sodium loads in addition to elevated blood pressure (see related article beginning on page 1244). A physiological role for uroguanylin is discussed, linking the intestine and kidney in an endocrine axis for the maintenance of sodium balance.
Leonard R. Forte
Stat3 is a vital transcription factor that is activated downstream of the gp130 receptor, primarily via IL-6 signaling in adult liver. A new study demonstrates that Stat3 provides hepatoprotection against Fas-mediated apoptotic liver damage by two mechanisms: direct inactivation of caspases and reduction of reactive oxygen species.
Rebecca Taub
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