IL-22, a vital cytokine in autoimmune diseases.

Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.

World Hepatitis day 2021 -screening and vaccination against Hepatitis B virus in Accra, Ghana.

BACKGROUND: In Ghana, Hepatitis B virus (HBV) infection remains a major public health threat as in many parts of the world. Even with an effective vaccine, there are shortfalls with low vaccine coverage among adults. To create awareness and encourage vaccination, community engagement and public-private partnerships are needed in endemic settings to help fund campaigns and offer screening and vaccinations at no cost to under privileged people. OBJECTIVES: An awareness and screening exercise was scheduled by University of Ghana-based Hepatitis-Malaria (HEPMAL) project team to coincide with the World Hepatitis Day (WHD) 2021. It was to engage the community in creating awareness of the menace and offer diagnostic services to ascertain prevalence levels and provide needed clinical support. METHODS: Participants from the University of Ghana community and its immediate environs were registered, taken through pre-counselling sessions where they were educated on hepatitis transmission and prevention before consenting. Eligible participants were screened for HBV markers (HBsAg, HBeAg, HBsAb, HBcAb,HbcAg) with a rapid test kit. All HBsAb-negative participants were recommended for initial vaccination at the event, whilst the subsequent shots were administered at the University Hospital Public Health Department. Hepatitis B surface Antigen-positive participants were counselled and referred for appropriate care. RESULTS: / Outcomes: A total of 297 people, comprising of 126 (42%) males and 171 (58%) females aged between 17 and 67 years were screened during the exercise. Amongst these, 246 (82.8%) showed no detectable protective antibodies against HBV and all of them agreed to and were given the first dose HBV vaccine. Additionally, 19 (6.4%) individuals tested positive for HBsAg and were counselled and referred to specialists from the University Hospital for further assessment and management. We found that 59 (19.9%) of our participants had previously initiated HBV vaccination and had taken at least one dose of the vaccine more than 6 months prior to this screening, 3 of whom tested positive for HBsAg. For the three-dose HBV vaccines deployed, a little over 20% (50/246) and a further 17% (33/196) did not return for the second and the third doses respectively, resulting in an overall 66% (163/246) of persons who completed all three vaccinations. CONCLUSIONS: / Lessons learnt: Our medical campaign exercise established an active case prevalence rate of 6.4% and achieved a full vaccination success rate of 66% which is critical in the induction of long-term immunity in the participants. Aside these achievements, we would like to reiterate the importance of the use of different approaches including educational events and WHD activities to target groups and communities to raise awareness. Additionally, home and school vaccination programmes may be adopted to enhance vaccine uptake and adherence to the vaccination schedule. We plan to extend this screening exercise to deprived and/or rural communities where HBV incidence may be higher than in urban communities.

CircRAPGEF5 acts as a modulator of RAS/RAF/MEK/ERK signaling during colorectal carcinogenesis.

Mutations in oncogenes such as KRAS, NRAS and BRAF promote the growth and survival of tumors, while excessive RAS/RAF/MEK/ERK activation inhibits tumor growth. In this study we examined the precise regulatory machinery that maintains a moderate RAS/RAF/MEK/ERK pathway activation during CRC. Here, using bioinformatic analysis, transcriptomic profiling, gene silencing and cellular assays we discovered that a circular RNA, circRAPGEF5, is significantly upregulated in KRAS mutant colorectal cancer (CRC) cells. CircRAPGEF5 suppressed mutant and constitutively activated KRAS and the expression of the death receptor TNFRSF10A. Silencing of circRAPGEF5-induced RAS/RAF/MEK/ERK signaling hyperactivation and apoptosis in CRC cells suggesting that an upregulation of circRAPEF5 may suppress the expression of TNFRSF10A and aid CRC progression by preventing apoptosis, while the direct interactions between circRAPGEF5 and elements of the RAS/RAF/MEK/ERK pathway was not identified, which nevertheless can be the basis for future research. Moreover, EIF4A3, was observed to share a similar expression pattern with circRAPEF5 and demonstrated to be a major controller of circRAPGEF5 via the promotion of circRAPGEF5 circularization and its silencing reduced circRAPGEF5 levels. Taken together, our findings reveal a mechanism of accurate RAS/RAF/MEK/ERK signaling regulation during CRC progression maintained by upregulation of circRAPGEF5 which may be a plausible target for future clinical applications that seek to induce CRC cell apoptosis via the RAS/RAF/MEK/ERK signaling pathway.

Reciprocal interactions between lncRNAs and MYC in colorectal cancer: partners in crime.

Proto-oncogenic MYC is frequently dysregulated in colorectal cancer (CRC). In the past decades, long noncoding RNAs (lncRNAs) have emerged as important regulators in cancers, acting as scaffolds, molecular decoys, post-transcriptional regulators, and others. Interestingly, lncRNAs are able to control MYC expression both at transcriptional and post-transcriptional levels. It is suggested that the reciprocal interaction of MYC and lncRNAs often occurs in CRC. MYC can affect the cell fate by promoting or inhibiting the transcription of some lncRNAs. At the same time, some lncRNAs can also affect MYC expression or transcriptional activity, and in turn decide the cell fate. In this review we summarized the current knowledge about the MYC and lncRNA axis, focusing on its mutual regulation, roles in CRC, and proposed potential therapeutic prospects for CRC treatment.

Expression patterns of immune checkpoint proteins and Plasmodium falciparum-induced cytokines in chronic hepatitis B virus-infected and uninfected individuals: A cross-sectional study.

Background and Aim: Chronic hepatitis B virus (CHB) infection remains a major public health problem. The American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidelines provide that CHB individuals not requiring antiviral therapy yet are monitored to determine the need for antiviral therapy in the future; however, these tests do not include measurement of cytokines and immune cell characterization. This case-control study compared the cytokine and immune checkpoint protein expression profiles between CHB individuals not yet on antiviral treatment and hepatitis B virus (HBV)-negative individuals. Methods: CD4 and CD8 T cells from CHB and HBV-negative individuals were characterized for immune checkpoint proteins programmed cell death-1 (PD1), T cell Immunoglobulin domain and mucin domain-containing protein 3 (TIM-3), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) (CD152), and a memory marker CXCR3 (CD183) using flow cytometry. Malaria-induced cytokine expression levels were determined by stimulating their blood cells with Plasmodium falciparum 3D7 strain antigens (CSP, AMA-1, and TRAP) in whole blood assays, and cytokine levels were measured using a 13-plex Luminex kit. Results: HBV-negative and CHB individuals had comparable levels of CD4+ and CD8+ T cells. However, a proportion of the CD4+ and CD8+ populations from both groups, which were CXCR3+, expressed PD-1 and CD152. The ability to produce cytokines in response to malaria antigen stimulation was not significantly different between the groups. Conclusion: These findings support excluding CHB individuals from antiviral therapy at this stage of infection. However, CHB individuals require regular monitoring to determine the need for later antiviral treatment.

Corrigendum: Asymptomatic Malaria Infection Is Maintained by a Balanced Pro- and Anti-inflammatory Response.

[This corrects the article DOI: 10.3389/fmicb.2020.559255.].

Asymptomatic Malaria Infection Is Maintained by a Balanced Pro- and Anti-inflammatory Response.

BACKGROUND: Pro- and anti-inflammatory cytokines are important mediators of immunity and are associated with malaria disease outcomes. However, their role in the establishment of asymptomatic infections, which may precede the development of clinical symptoms, is not as well-understood. METHODS: We determined the association of pro and anti-inflammatory cytokines and other immune effector molecules with the development of asymptomatic malaria. We measured and compared the plasma levels of pro-inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-6, IL-12p70, IL-17A, and granzyme B, the anti-inflammatory cytokine IL-4 and the regulatory cytokine IL-10 from children with asymptomatic malaria infections (either microscopic or submicroscopic) and uninfected controls using Luminex. RESULTS: We show that individuals with microscopic asymptomatic malaria had significantly increased levels of TNF-α and IL-6 compared to uninfected controls. Children with either microscopic or submicroscopic asymptomatic malaria exhibited higher levels of IFN-γ, IL-17A, and IL-4 compared to uninfected controls. The levels of most of the pro and anti-inflammatory cytokines were comparable between children with microscopic and submicroscopic infections. The ratio of IFN-γ/IL-10, TNF-α/IL-10, IL-6/IL-10 as well as IFN-γ/IL-4 and IL-6/IL-4 did not differ significantly between the groups. Additionally, using a principal component analysis, the cytokines measured could not distinguish amongst the three study populations. This may imply that neither microscopic nor submicroscopic asymptomatic infections were polarized toward a pro-inflammatory or anti-inflammatory response. CONCLUSION: The data show that asymptomatic malaria infections result in increased plasma levels of both pro and anti-inflammatory cytokines relative to uninfected persons. The balance between pro- and anti-inflammatory cytokines are, however, largely maintained and this may in part, explain the lack of clinical symptoms. This is consistent with the generally accepted observation that clinical symptoms develop as a result of immunopathology involving dysregulation of inflammatory mediator balance in favor of pro-inflammatory mediators.