Effect of M2 macrophage adoptive transfer on transcriptome profile of injured spinal cords in rats

The previous studies showed that alternatively activated anti-inflammatory macrophage (M2) adoptive immunity can improve the proportion of local M2 cells and play the neuroprotective effect after spinal cord injury (SCI). Its molecular mechanism is not yet very clear. Therefore, this study aims to analyze the effect of the M2 adoptive transfer on the local expression of gene transcription. Sprague-Dawley (SD) rats were used for culture of macrophages and establishment of SCI models. After SCI, the polarized M2 macrophages were transferred to the injured rats by tail vein injection. Seven days after operation, the differentially expressed genes (DEGs) in the spinal cords were analyzed by RNA-sequencing (RNA-Seq). Then, the functional enrichment analysis and pathways were performed by using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), respectively. RNA-Seq showed that M2 adoptive immunity can down-regulate many well-studied gene expressions associated with signaling pathways of inflammatory, such as antigen processing and presentation, phagosome, cell adhesion molecules, natural killer cell-mediated cytotoxicity, endocytosis, proteasome, and Toll-like receptor signaling pathway. These may explain the mechanism of our previous adoptive immunization of M2 cells to provide neuroprotection for SCI. In addition, a novel pathway, retinoic acid-inducible gene-1 (RIG-I)-like receptor signaling pathway was found to be involved in the pathological process of SCI and the response to M2 adoptive immunity as well. This will provide a new explanation for the pathological mechanism of SCI and a new theoretical and experimental basis for its clinical treatment. The raw Illumina data are available at http://www.ncbi.nlm.nih.gov/sra (accession number PRJNA517238). Impact statement This research aimed to analyze the effect of M2 macrophage adoptive transfer on the local expression of gene transcription after SCI by RNA-Seq. The results showed that M2 adoptive immunity can down-regulate many well-studied gene expressions associated with signaling pathways of inflammatory. These may explain the mechanism of our previous adoptive immunization of M2 cells to provide neuroprotection for SCI. In addition, a novel pathway, RIG-I-like receptor signaling pathway was also found to involve in the pathological process of SCI and the response to M2 adoptive immunity. This will provide a new explanation for the pathological mechanism of SCI and a new theoretical and experimental basis for its clinical treatment.

Management of celiac disease: from evidence to clinical practice

Celiac disease (CD) is a complex polygenic disorder, which involves genetic factors human leukocyte complex (HLA) and non-HLA genes, environmental factors, innate and adoptive immunity, and a robust chronic T-mediated autoimmune component. The main goal of the present monograph is to define a methodological approach for the disease, characterized by frequent late diagnosis, in order for the physician to become aware of the disease management, the diversity of the clinical presentation itself and in different patients. A unique attention is payed to the specific diagnostic tests to define a correct and accurate application of them, and in addition, to disease follow-up and possible complications. Moreover, a dedicated space is assigned to refractory CD, to potential CD and non-celiac gluten sensitivity. Legislative aspects of the celiac disease in Italy are addressed, too. The celiac disease guidelines and their evaluation by means of Appraisal of Guidelines, Research and Evaluation II instrument allow us to classify the different recommendations and to apply them according to the stakeholders’ involvement, pertinence, methodological accuracy, clarity and publishing independence. Finally, the most current scientific evidence is taken into account to create a complete updated monograph.

Kunkel Lecture: Fundamental immunodeficiency and its correction

“Fundamental immunodeficiency” is the inability of the encoded immune system to protect an otherwise healthy host from every infection that could threaten its life. In contrast to primary immunodeficiencies, fundamental immunodeficiency is not rare but nearly universal. It results not from variation in a given host gene but from the rate and extent of variation in the genes of other organisms. The remedy for fundamental immunodeficiency is “adopted immunity,” not to be confused with adaptive or adoptive immunity. Adopted immunity arises from four critical societal contributions to the survival of the human species: sanitation, nutrition, vaccines, and antimicrobial agents. Immunologists have a great deal to contribute to the development of vaccines and antimicrobial agents, but they have focused chiefly on vaccines, and vaccinology is thriving. In contrast, the effect of antimicrobial agents in adopted immunity, although fundamental, is fragile and failing. Immunologists can aid the development of sorely needed antimicrobial agents, and the study of antimicrobial agents can help immunologists discover targets and mechanisms of host immunity.

ANTI-TUMOR RESPONSES INDUCED BY LASER IRRADIATION AND IMMUNOLOGICAL STIMULATION USING A MOUSE MAMMARY TUMOR MODEL

Anti-tumor immunological response induced by local intervention is ideal for treatment of metastatic tumors. Laser immunotherapy was developed to synergize photothermal interaction with immunological stimulation for cancer treatment. Using an infrared laser, indocyanine green (ICG, as a light absorbing agent), and glycated chitosan (GC, as an immunostimulant), laser immunotherapy has resulted in tumor suppression and anti-tumor responses in pre-clinical as well as clinical studies. To further understand the mechanism of laser immunotherapy, the effects of laser and GC treatment without specific enhancement of laser absorption were studied. Passive adoptive immunity transfer was performed using splenocytes as immune cells. Spleen cells harvested from tumor-bearing mice treated by laser + GC provided 60% immunity in naive recipients. Furthermore, cytotoxicity and TNF-α secretion by splenocytes from treated mice also indicated that laser + G induced immunity was tumor-specific. The high level of infiltrating T cells in tumors after laser + GC treatment further confirmed a specific anti-tumor immune response. Therefore, laser + GC could prove to be a promising selective local treatment modality that induces a systemic anti-tumor response, with appropriate laser parameters and GC doses.

A Key Role for NF-κB Transcription Factor c-Rel in T-Lymphocyte-Differentiation and Effector Functions

The transcription factors of the Rel/NF-κB family function as key regulators of innate and adoptive immunity. Tightly and temporally controlled activation of NF-κB-signalling pathways ensures prevention of harmful immune cell dysregulation, whereas a loss of control leads to pathological conditions such as severe inflammation, autoimmune disease, and inflammation-associated oncogenesis. Five family members have been identified in mammals: RelA (p65), c-Rel, RelB, and the precursor proteins NF-κB1 (p105) and NF-κB2 (p100), that are processed into p50 and p52, respectively. While RelA-containing dimers are present in most cell types, c-Rel complexes are predominately found in cells of hematopoietic origin. In T-cell lymphocytes, certain genes essential for immune function such asIl2andFoxp3are directly regulated by c-Rel. Additionally, c-Rel-dependent IL-12 and IL-23 transcription by macrophages and dendritic cells is crucial for T-cell differentiation and effector functions. Accordingly, c-Rel expression in T cells and antigen-presenting cells (APCs) controls a delicate balance between tolerance and immunity. This review gives a selective overview on recent progress in understanding of diverse roles of c-Rel in regulating adaptive immunity.