Autoimmunity

Association of BAFF/BLyS overproduction and altered B-cell differentiation with Sjögren's syndrome. Groom, J. et al. J. Clin. Invest. 109, 59–68 (2002) [PubMed].

Sjögren's syndrome (SS) is a chronic autoimmune disorder that causes a dry mouth and eyes. It is associated with B-cell hyperactivity and serum autoantibodies. BAFF-transgenic mice develop a lupus-like disorder. This paper shows that ageing BAFF-Tg mice develop a pathology that resembles SS. Marginal-zone-like B cells were identified in salivary glands of BAFF-Tg mice. Humans with SS have elevated levels of circulating BAFF, perhaps because of an imbalance in BAFF production.

Innate immunity

Human macrophage activation programmes induced by bacterial pathogens. G. J. Nau et al. Proc. Natl Acad. Sci. USA 22nd January 2002 (epub ahead of print).

Although the innate immune system is not 'specific', there are indications that it can differentiate between different classes of bacteria. Here, the responses of macrophages to three classes of bacteria (Gram-negative, Gram-positive and mycobacteria) were compared using genome-wide gene expression profiling. A common activation programme of gene expression (132 induced and 59 repressed genes) was identified. Pathogen-specific responses were also identified, such as the repression of IL-12 by Mycobacterium tuberculosis.

Cytokine signalling

Physical and functional interaction between GATA-3 and Smad3 allows TGF-β regulation of GATA target genes. Blokzijl, A. et al. Curr. Biol. 12, 35–45 [PubMed]

GATA-3 is a master transcriptional activator of CD4+ TH2-cell differentiation. TGF-β has complex effects on T-cell differentiation and has been proposed to inhibit TH2 differentiation by inhibiting GATA-3 production. Here, Blokzijl, A. et al. reveal a new interface between TGF-β and GATA-3. They show that smad 3 (a crucial TGF-β signal transducer) interacts physically with GATA-3 to form a complex that can regulate the transcription of TH2 cytokine genes.

Immune regulation

TH2 response induction by dendritic cells: a role for CD40 MacDonald, A.S. et al. J. Immunol. 168, 537–540 2002 [PubMed]

Dendritic cells are thought to be key regulators of TH1–TH2 differentiation during CD4+ T-cell priming. They interpret microbial signals and relay them to T cells through accessory molecules (such as CD40). However, most work has focused on the induction of TH1 cells. By adoptive transfer of CD40-deficient dendritic cells that have been primed with TH1- or TH2-inducing microbial stimuli, MacDonald et al. shows a crucial role for CD40–CD40L interactions in the induction of TH2, but not TH1, responses.