A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells.

Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host

Chymotrypsin mRNA expression in digestive gland amoebocytes: cell specification occurs prior to metamorphosis and gut morphogenesis in the gastropod Haliotis rufescens

In the non-feeding larva of the marine gastropod, Haliotis rufescens, gut morphogenesis is initiated at metamorphosis. Intestine-specific chymotrypsin gene expression begins in amoebocytes located in the dorsoposterior region of the undifferentiated digestive gland prior to metamorphosis, 5 d post-fertilization. Transcript accumulates steadily in these cells over the next 6 d while the amoebocytes migrate slowly dorsally. Induction of metamorphosis dramatically accelerates the rates of chymotrypsin mRNA accumulation and amoebocyte migration, and is required for homing of the amoebocytes to the hindgut region. Induction of chymotrypsin gene expression occurs only in larvae that had developed competence to recognize an exogenous morphogenetic cue and initiate metamorphosis, with a more pronounced increase in chymotrypsin mRNA accumulation in occurring older larvae. Chymotrypsin mRNA accumulation patterns suggest that hindgut cell specification occurs prior to metamorphosis, but that completion of the morphogenetic program requires signaling events associated with metamorphosis

Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A) in the ACVR1 gene in almost all patients reported. Very recently two other mutations have been described in three FOP patients. We present here evidence for two further unique mutations (c.605G>T and c.983G>A) in this gene in two FOP patients with some atypical digit abnormalities and other clinical features. The observation of disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation and provides a potential rationale for phenotypic variation