Trasplante pulmonar: una perspectiva desde la inmunología / Lung transplantation: a perspective from immunology

Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.

Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.

Differential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3.

Bipolar disorder (BD) is a severe mental illness with a strong genetic component. Despite its high degree of heritability, current genetic studies have failed to reveal individual loci of large effect size. In lieu of focusing on individual genes, we investigated regulatory units (regulons) in BD to identify candidate transcription factors (TFs) that regulate large groups of differentially expressed genes. Network-based approaches should elucidate the molecular pathways governing the pathophysiology of BD and reveal targets for potential therapeutic intervention. The data from a large-scale microarray study was used to reconstruct the transcriptional associations in the human prefrontal cortex, and results from two independent microarray data sets to obtain BD gene signatures. The regulatory network was derived by mapping the significant interactions between known TFs and all potential targets. Five regulons were identified in both transcriptional network models: early growth response 3 (EGR3), TSC22 domain family, member 4 (TSC22D4), interleukin enhancer-binding factor 2 (ILF2), Y-box binding protein 1 (YBX1) and MAP-kinase-activating death domain (MADD). With a high stringency threshold, the consensus across tests was achieved only for the EGR3 regulon. We identified EGR3 in the prefrontal cortex as a potential key target, robustly repressed in both BD signatures. Considering that EGR3 translates environmental stimuli into long-term changes in the brain, disruption in biological pathways involving EGR3 may induce an impaired response to stress and influence on risk for psychiatric disorders, particularly BD.