Clinical and Experimental Immunology

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ISSN / EISSN : 0009-9104 / 1365-2249
Published by: Oxford University Press (OUP) (10.1093)
Total articles ≅ 15,118
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Sigal Matza Porges,
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac089

Abstract:
Approximately 10% of cancers have a hereditary predisposition. However, no genetic diagnosis is available in 60%-80% of familial cancers. In some of these families, immune dysregulation-mediated disease is frequent. The immune system plays a critical role in identifying and eliminating tumors; thus, dysregulation of the immune system can increase the risk of developing cancer. This review focuses on some of the genes involved in immune dysregulation the promote the risk for cancer. Genetic counseling for patients with cancer curently focuses on known genes that raise the risk of cancer. In missing hereditary familial cases, the history family of immune dysregulation should be recorded, and genes related to the immune system should be analyzed in relevant families. On the other hand, patients with immune disorders diagnosed with a pathogenic mutation in an immune regulatory gene may have an increased risk of cancer. Therefore, those patients need to be under surveillance for cancer. Gene panel and exome sequencing are currently standard methods for genetic diagnosis, providing an excellent opportunity to jointly test cancer and immune genes.
Wei Sun, Yan Feng, Hui Li, Xiaoqing He, Yihan Lu, Zhongyan Shan, ,
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac086

Abstract:
Anti-alpha-enolase autoantibodies have not only been found to play an important role in autoimmune diseases, but also cause neurological damage in adults. In this study, a pregnant mouse model with high serum alpha-enolase (ENO1)-specific antibody (ENO1Ab) was established by immunization with ENO1 protein to explore the effects of maternal circulatory ENO1Ab on the brain development in offspring. The pups showed impaired learning and memory abilities with obviously thinner tight junctions in the brain tissue. IgG deposits colocalized with both ENO1 protein and complement 3 (C3), and the membrane attack complex was obviously detectable in the brain tissues of pups from dams with high serum ENO1Ab expression. Our findings suggest that highly-expressed ENO1Ab in the maternal circulation can pass through the blood-placenta-barrier and the compromised blood-brain barrier into the brain tissues of offspring, and may cause neurological development impairment mainly through complement-dependent cytotoxicity.
Atte Valli, Krista Kuuliala, Anniina Virtanen, Antti Kuuliala, Maaria Palmroth, Ritva Peltomaa, Krista-Liisa Vidqvist, , Olli Silvennoinen,
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac085

Abstract:
The data on effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analysed how tofacitinib treatment and thus inhibition of the Janus kinase – signal transducer and activation on transcription pathway affects the in vivo levels of inflammation-related plasma proteins in RA patients. In this study, sixteen patients with active RA [28-joint Disease Activity Score (DAS28) >3.2] despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) started tofacitinib treatment 5mg twice daily. Levels of 92 inflammation-related plasma proteins were determined by proximity extension assay at baseline and at three months. Tofacitinib treatment for three months, in csDMARD background, decreased mean DAS28 from 4.4 to 2.6 (p20%) and statistically significant (p50%) decrease was observed for interleukin-6 (IL-6), C-X-C motif chemokine ligand 1, matrix metalloproteinase-1 and AXIN1. Higher baseline level of IL-6, and lower levels of C-C motif chemokine 11 and Delta and Notch-like epidermal growth factor-related receptor were associated with DAS28 improvement. Our results indicate that tofacitinib downregulates several proinflammatory plasma proteins which may contribute to the clinical efficacy of tofacitinib. In addition, soluble biomarkers may predict the treatment response to tofacitinib.
Anne B Kristensen, Kathleen Wragg, Hillary Vanderven, Wen Shi Lee, Julie Silvers, Helen E Kent, Michael D Grant, Anthony D Kelleher, Jennifer A Juno, Stephen J Kent, et al.
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac082

Abstract:
Natural killer (NK) cells are important anti-viral effector cells. The function and phenotype of the NK cells that constitute an individual’s NK cell repertoire can be influenced by ongoing and/or previous viral infections. Indeed, infection with human cytomegalovirus (HCMV) drives the expansion of a highly differentiated NK cell population characterized by expression of CD57 and the activating NKG2C receptor. This NK cell population has also been noted to occur in HIV-1-infected individuals. We evaluated the NK cells of HIV-1-infected and –uninfected individuals to determine the relative frequency of highly differentiated CD57 +NKG2C + NK cells and characterize these cells for their receptor expression and responsiveness to diverse stimuli. Highly differentiated CD57 +NKG2C + NK cells occurred at higher frequencies in HCMV-infected donors relative to HCMV-uninfected donors and were dramatically expanded in HIV-1/HCMV co-infected donors. The expanded CD57 +NKG2C + NK cell population in HIV-1-infected donors remained stable following antiretroviral therapy. CD57 +NKG2C + NK cells derived from HIV-1-infected individuals were robustly activated by antibody-dependent stimuli that contained anti-HIV-1 antibodies or therapeutic anti-CD20 antibody, and these NK cells mediated cytolysis through NKG2C. Lastly, CD57 +NKG2C + NK cells from HIV-1-infected donors were characterized by reduced expression of the inhibitory NKG2A receptor. The abundance of highly functional CD57 +NKG2C + NK cells in HIV-1-infected individuals raises the possibility that these NK cells could play a role in HIV-1 pathogenesis or serve as effector cells for therapeutic/cure strategies.
Katherine E Olson, R L Mosley, Howard E Gendelman
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac084

Abstract:
While inflammation may not be the cause of disease, it is well known that it contributes to disease pathogenesis across a multitude of peripheral and central nervous system disorders. Chronic and overactive inflammation due to an effector T cell-mediated aberrant immune response ultimately leads to tissue damage and neuronal cell death. To counteract peripheral and neuroinflammatory responses, research is being focused on regulatory T cell enhancement as a therapeutic target. Regulatory T cells are an immunosuppressive subpopulation of CD4+ T helper cells essential for maintaining immune homeostasis. The cells play pivotal roles in suppressing immune responses to maintain immune tolerance. In so doing, they control T cell proliferation and pro-inflammatory cytokine production curtailing autoimmunity and inflammation. For nervous system pathologies, Treg are known to affect the onset and tempo of neural injuries. To this end, we review recent findings supporting Treg’s role in disease, as well as serving as therapeutic agents in multiple sclerosis, myasthenia gravis, Guillain-Barre syndrome, Parkinson’s and Alzheimer’s diseases, and amyotrophic lateral sclerosis. An ever-broader role for Treg in control of neurologic disease has been shown for traumatic brain injury, stroke, neurotrophic pain, epilepsy, and psychiatric disorders. To such ends, this review serves to examine the role played by Tregs in nervous system diseases with a focus on harnessing their functional therapeutic role(s).
Correction
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac081

Abstract:
This is a correction to: Mauro Corrado, Diana Moreira, Nicholas Jones, Metabolites: fuelling the immune response, Clinical and Experimental Immunology, Volume 208, Issue 2, May 2022, Pages 129–131, https://doi.org/10.1093/cei/uxac053
Pablo J Bertrand, Yaneisi Vázquez, Andrea A Beckhaus, Liliana A González, Ana María Contreras, Marcela Ferrés, Oslando Padilla, Claudia A Riedel, Alexis M Kalergis,
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac083

Abstract:
Lower respiratory tract infections (LRTIs) produced by viruses are the most frequent cause of morbidity and mortality in children younger than 5 years of age. The immune response triggered by viral infection can induce a strong inflammation in the airways and cytokines could be considered as biomarkers for disease severity as these molecules modulate the inflammatory response that defines the outcome of patients. Aiming to predict the severity of disease during respiratory tract infections, we conducted a 1-year follow-up observational study in infants who presented upper or lower respiratory tract infections caused by seasonal respiratory viruses. At the time of enrollment, nasopharyngeal swabs (NPS) were obtained from infants to measure mRNA expression and protein levels of IL-3, IL-8, IL-33, and thymic stromal lymphopoietin. While all cytokines significantly increased their protein levels in infants with upper and lower respiratory tract infections as compared to control infants, IL-33 and IL-8 showed a significant increase in respiratory syncytial virus (RSV)-infected patients with LRTI as compared to patients with upper respiratory tract infection. We also found higher viral loads of RSV-positive samples with a greater IL-8 response at the beginning of the symptoms. Data obtained in this study suggest that both IL-8 and IL-33 could be used as biomarkers for clinical severity for infants suffering from LRTIs caused by the RSV.
Mariska Kerstholt, Freek R van de Schoor, Marije Oosting, Simone J C F M Moorlag, Yang Li, Martin Jaeger, Wouter A van der Heijden, Rahajeng N Tunjungputri, Jéssica C dos Santos, Brenda Kischkel, et al.
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac073

Abstract:
Previous studies have shown that monocytes can be ‘trained’ or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals.
Peixuan Han, Liping Chen, Dong Chen, Ruiming Yang, Wei Wang, Jingyu Liu, Shaoheng He,
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac074

Abstract:
Increased expression of substance P (SP) and neurokinin-1 receptor (NK1R) has been noticed in patients with allergic rhinitis (AR) and allergic asthma (AA). However, little is known of the expression of SP and NK1R in monocytes and B cells of AR and AA. In the present study, the expression levels of SP and NK1R were determined by flow cytometry and mouse AR and AA models. The results showed that both percentages of SP + monocytes and SP + B cells, and mean fluorescence intensity (MFI) of SP in monocytes were elevated in the blood of AA and AR combined with AA (ARA) patients. Similarly, the percentages of NK1R + monocytes were elevated in the blood of AR, AA and ARA patients. Allergens artemisia sieversiana wild allergen extract (ASWE), house dust mite extract (HDME) and platanus pollen allergen extract (PPE) increased the expression density of SP molecules (determined by MFI) in an individual monocyte of AR patients. HDME and PPE appeared to enhance SP and NK1R expression in the B cells of ARA and AR patients. In the mouse AR and AA models, the percentages of NK1R + monocytes and B cells were elevated in blood following OVA sensitization and challenge. Knocking out the FcεRI molecule completely abolished the OVA-induced upregulation of expression of NK1R in monocytes and B cells of AA mice. In conclusion, upregulated expressions of SP and NK1R may contribute to the pathogenesis of airway allergy.
S Alice Long,
Clinical and Experimental Immunology; https://doi.org/10.1093/cei/uxac077

Abstract:
Type 1 diabetes (T1D) is an autoimmune disease resulting in destruction of the insulin-producing pancreatic beta cells. Disease progression occurs along a trajectory from genetic risk, the development of islet autoantibodies and autoreactive T cells ultimately progressing to clinical disease. Natural history studies and mechanistic studies linked to clinical trials have provided insight into the role of the immune system in disease pathogenesis. Here, we review our current understanding of the underlying etiology of T1D, focusing on the immune cell types that have been implicated in progression from pre-symptomatic T1D to clinical diagnosis and established disease. This knowledge has been foundational for the development of immunotherapies aimed at prevention and treatment of T1D.
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