A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of non-polymorphic KLR in “higher” primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire

The Gene Ontology: enhancements for 2011

The Gene Ontology (GO) (http://www.geneontology.org) is a community bioinformatics resource that represents gene product function through the use of structured, controlled vocabularies. The number of GO annotations of gene products has increased due to curation efforts among GO Consortium (GOC) groups, including focused literature-based annotation and ortholog-based functional inference. The GO ontologies continue to expand and improve as a result of targeted ontology development, including the introduction of computable logical definitions and development of new tools for the streamlined addition of terms to the ontology. The GOC continues to support its user community through the use of e-mail lists, social media and web-based resources

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis Dermatite atópica: implicações clínicas de avanços recentes na patogênese

Atopic dermatitis is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10-20 of infants and 1-3 of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. Probably half of the children with atopic dermatitis develop some other form of atopic disease later in life. The pathogenesis involves a complex interplay of factors including genetic predisposition due to altered immune or skin barrier function, interactions with the environment such as food and allergen exposures, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of atopic dermatitis and how insights provide new therapeutic potential for its treatment.<br>A dermatite atópica é uma doença cutânea inflamatória crônica cuja prevalência tem aumentado de forma constante, afetando 10-20% dos lactentes e 1-3% dos adultos em todo o mundo. Ela é freqüentemente a primeira manifestação clínica de doença atópica, precedendo a asma e a rinite alérgica. Provavelmente metade das crianças com dermatite atópica desenvolvem alguma outra forma de doença atópica em outras fases da vida. A patogenia envolve uma interação complexa entre fatores que incluem predisposição genética devido a uma função alterada da barreira cutânea ou imunológica, interações com o ambiente, tais como exposição a alimentos e alergenos, e desencadeadores infecciosos de inflamação. Nesta revisão, resumimos os avanços recentes na compreensão da contribuição de diferentes fatores à fisiopatologia da dermatite atópica e como os novos conhecimentos proporcionam novo potencial terapêutico