In the present issue, we continue our recently initiated journey in the world of miRNAs with an exciting review by Dr. Carlo Croce and collaborators, featuring a novel star on the sky of immune regulation, namely miR-155. Since its discovery, this intriguing molecule posed several challenges in terms of its role in the physiology of immune response, inflammation, and cancer. Most notably, the observation that miR-155 is highly upregulated in lymphocytes during a normal immune response without pathologic consequences, while transgenic expression of moderate levels of miR-155 results in lymphoid malignancies, provides a tantalizing insight into the complexity of the miRNA regulatory network. Tili et al. propose that the miR-155 expression must be tightly regulated—in normal circumstances—to achieve fine-tuning of lymphocyte homeostasis and limit chronic inflammation, thus diminishing the risk of oncogenesis. In addition, the authors proposed that miR-155 is a potential therapeutic target once we understand, first, how to safely modulate miRNA's levels and second, what the expression levels are that need to be achieved to suppress desired pathologies.
Also, in this issue we host a comprehensive review describing exciting efforts to energize and spearhead new vaccine design and development for HIV. The authors, led by Dr. Barbara Ensoli, justifiably argue that despite developments in the area of small molecules against HIV, this virus remains a world-wide threat warranting successful efforts in designing prophylactic and therapeutic vaccines. The authors outline the merits of non-structural virion antigens—such as Tat—as logical vaccine components based on their biological role connected with virus replication and infectivity, sequence conservation, and even adjuvanticity. The highlighted approach is a multivalent one, resulting from the addition of Tat to envelope antigen (Env) potentially resulting in increased anti-viral immunity and cross-clade protection. The upcoming years will certainly yield very important results from current and upcoming trials exploring monovalent and multivalent HIV vaccines designed using this principle—but a close cooperation between non-profit organizations, biopharmaceutical companies, and governmental organizations will be absolutely key to ensure progress in this area.
Further, Dr. Nima Rezaei and co-authors approach a rather difficult area—that of primary immunodeficiency diseases (PID) encompassing neutropenia. These genetic afflictions are considerably heterogenic and are associated with quite diverse pathologies, from recurring infections to inflammation, cancer, and hematological disorders. More recently, there has been significant progress in understanding the molecular pathology of neutropenias in man, with the discovery of genetic deficiencies involving p14, HAX1, or AK2 genes. Clinical, immunological, and genetic features of neutropenia are highlighted in this review.
In another review focused on an entirely different area, transplantation immunology, Dr. Suping Li and co-authors tackle the mechanism of Rapamycin—induced tolerance to allografts. Rapamycin is one of the agents capable of delivering proliferation signal inhibition (PSI) and has been thought to induce tolerance against donor antigens via upregulating Treg cells. Nevertheless, Dr. Li et al. discuss emerging evidence questioning this model and advancing complementary or alternate explanations in support of the mechanism of action of proliferation signal inhibitors such as Rapamycin. In the end, this review raises many more questions but its aim is to raise awareness on this important issue in the field of transplantation immunology, to be elucidated in the future.
We are closing this issue with another review by Dr. Fang Zhou, presenting a state of the art review in the area of viral immune evasion. This review discusses the delicate balance between viruses and immunity, emphasizing the multifaceted mechanisms deployed by a wide range of viruses to interfere with adaptive immunity. The focus of the review is mostly on viral inhibition of MHC class I expression, antigenic peptide generation, and MHC-restricted presentation—all critical events leading to a successful immune response.
In the upcoming issues, we are shifting gears to several areas such as the mechanisms underlying immune homeostasis, acting systemically (for example Tregs) or at mucosal surfaces such as the intestinal tract. We will continue to feature, also, original reviews and editorials in basic and translational immunology—relevant to inflammation, cancer, infectious diseases, and vaccines.