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 as Il2 and Foxp3 are 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.
The immunoproteasome subunit β5i has been shown to play an important role in Th1/Th17 driven models of colitis and arthritis. However, the function of β5i in Th2 dependent diseases remains enigmatic. To study the role of β5i in Th2-driven pathology, β5i knockout (KO) and control mice were tested in different models of experimental allergic asthma. β5i-deficient mice showed reduced OVA/Alum- and subcutaneous/OVA-induced acute asthma with decreased eosinophilia in the bronchoalveolar lavage (BAL), low OVA-specific IgG1 and reduced local and systemic Th2 cytokines. While Th2 cells in the lungs were reduced, Tregs and Th1 cells were not affected. Attenuated asthma in β5i KO mice could not be attributed to defects in OVA uptake or maturation of dendritic cells in the lung. Surprisingly, β5i deficient mice developed HDM asthma which was comparable to control mice. Here, we present novel evidence for the requirement of the β5i immunosubunit to generate a strong Th2 response during OVA- but not HDM-induced acute asthma. The unexpected role of β5i in OVA asthma remains to be clarified.
Paratonsillitis is one of the most common purulent inflammatory diseases, considered as a manifestation of chronic tonsillitis. The aim of the work is to study the state of local immunity by the level of immunoglobulin A in saliva in patients with paratonsillitis and its changes in the treatment process, to determine the level of antistreptolysin-O in serum, as well as to study the etiological factors of paratonsillites in the microbiological assessment of the species composition of flora in smears from the cavity of paratonsillar abscess. Under our observation there were 152: 32 healthy people and 120 patients with paratonsillitis under abecedarian or abscess stage. It was found that in patients with paratonsillitis there is a significant (p<0.001) decrease in the level of secretory immunoglobulin A in saliva, which indicates a violation of local immunity and requires correction. The level of antibodies to streptolysin-O in the serum of patients with paratonsillitis was significantly - 10.25 times higher than in healthy individuals in the control group, which confirms the high streptococcal antigenic load. The results of microbiological examination of smears from the abscess cavity indicated the release of the most frequent pathogens of paratonsillites - Streptococcus β-haemolythicus, Streptococcus Pneumoniae and Staphylococcus Aureus, with bacterial associations prevailing (63.5%). After a course of antimicrobial therapy, supplemented with immunomodulatory agents in the form of bacterial lysates, there was an increase in the level of secretory IgA in saliva in 10-30 days in 3.3-4.5 times. At the same time, the level of antistreptolysin-O significantly decreased. In patients receiving immunomodulatory therapy in the form of bacterial lysates in the complex treatment of paratonsillitis, for the period of observation of 6 months, there was a decrease in the frequency of relapses of the disease by 2 times.
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