Insight Into Non-Pathogenic Th17 Cells in Autoimmune Diseases

Wu, Xinyu; Tian, Jie; Wang, Shengjun

doi:10.3389/fimmu.2018.01112

Cited by 110 publications

(91 citation statements)

References 74 publications

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“…Thus, Th17 producing IL-10 cells appears to act as a double-edged sword in the pathogenesis of various diseases. Several studies indicated that Th17 cells can trans -differentiate into a Th1 or Th2 cell phenotype, thus the plasticity of Th17 cells may be dependent on the dominant factor in the surrounding milieu ( Zielinski et al, 2012 ; Wu et al, 2018 ). In addition, our findings are in agreement with Camargo et al (2018) that also demonstrated the increase of IL-10 in the group of animals exposed to ovalbumin.…”

Section: Discussionmentioning

confidence: 99%

Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma

et al. 2018

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Background: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for the treatment of this disease.Objective: To study the effects of an anti-IL17 neutralizing antibody and ROCK inhibitor treatments, separately and in combination, in a murine model of chronic allergy-induced lung inflammation.Methods: Sixty-four BALBc mice, were divided into eight groups (n = 8): SAL (saline-instilled); OVA (exposed-ovalbumin); SAL-RHOi (saline and ROCK inhibitor), OVA-RHOi (exposed-ovalbumin and ROCK inhibitor); SAL-anti-IL17 (saline and anti-IL17); OVA-anti-IL17 (exposed-ovalbumin and anti-IL17); SAL-RHOi-anti-IL17 (saline, ROCK inhibitor and anti-IL17); and OVA-RHOi-anti-IL17 (exposed-ovalbumin, anti-IL17, and ROCK inhibitor). A 28-day protocol of albumin treatment was used for sensitization and induction of pulmonary inflammation. The anti-IL17A neutralizing antibody (7.5 μg per treatment) was administered by intraperitoneal injection and ROCK inhibitor (Y-27632) intranasally (10 mg/kg), 1 h prior to each ovalbumin challenge (days 22, 24, 26, and 28).Results: Treatment with the anti-IL17 neutralizing antibody and ROCK inhibitor attenuated the percentage of maximal increase of respiratory system resistance and respiratory system elastance after challenge with methacholine and the inflammatory response markers evaluated (CD4+, CD8+, ROCK1, ROCK2, IL-4, IL-5, IL-6, IL-10 IL-13, IL-17, TNF-α, TGF-β, NF-κB, dendritic cells, iNOS, MMP-9, MMP-12, TIMP-1, FOXP3, isoprostane, biglycan, decorin, fibronectin, collagen fibers content and gene expression of IL-17, VAChT, and arginase) compared to the OVA group (p < 0.05). Treatment with anti-IL17 and the ROCK inhibitor together resulted in potentiation in decreasing the percentage of resistance increase after challenge with methacholine, decreased the number of IL-5 positive cells in the airway, and reduced, IL-5, TGF-β, FOXP3, ROCK1 and ROCK2 positive cells in the alveolar septa compared to the OVA-RHOi and OVA-anti-IL17 groups (p < 0.05).Conclusion: Anti-IL17 treatment alone or in conjunction with the ROCK inhibitor, modulates airway responsiveness, inflammation, tissue remodeling, and oxidative stress in mice with chronic allergic lung inflammation.

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Section: Discussionmentioning

confidence: 99%

Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma

et al. 2018

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“…For example, the canonical clock gene Rora is required for the differentiation of type 2 innate lymphoid cells (ILC2s), which play a role in type II inflammation, allergy, and defense against parasites (59). A splice variant of the clock gene Rorg (Rorgt) is critical for the development of type 3 innate lymphoid cells (ILC3s), lymphoid tissue inducer (LTi) cells, and the CD4 + T helper cell subset Th17 cells (60)(61)(62). Rora is also important for the full development of Th17 cells (63).…”

Section: Clocks and Immunitymentioning

confidence: 99%

Perfect timing: circadian rhythms, sleep, and immunity — an NIH workshop summary

et al. 2020

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Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses-ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation-are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, sleep, and immune regulation. Circadian rhythms are daily variations in behavior and biological activity that stem from an intrinsic ability of organisms to align themselves with the environmental 24-hour light/dark cycle. These rhythms originate from an internal biological clock that drives many aspects of human physiology, including the sleepwake cycle and daily variations in blood pressure, body temperature, and cortisol (1). A growing body of epidemiological evidence demonstrates an association between altering circadian timing through shift work or frequent time zone travel and increased rates of cardiovascular disorders, metabolic syndrome, and cancer (2-4). Clinical aspects of disease such as pain perception, asthma exacerbations, and myocardial infarctions are more common at certain times of day or night (5, 6). The discovery of the genetic basis for the circadian clock in the 1980s and 1990s has ushered in a new era in which long-appreciated circadian rhythms in physiology and clinical medicine are being reframed in terms of gene expression, metabolism, signal transduction, and cellular physiology (7). The translation of circadian discovery into strategies to improve the prevention and management of disease promises to be transformative, but at present, fundamental research is outpacing clinical application (Figure 1A). Much will depend on research identifying the critical mechanisms and targets to which circadian rhythm-based therapeutic strategies can be applied. An emerging example of exciting circadian discovery with potential clinical relevance is the intersection between circadian function and immune regulation (Figure 1B). The NIH recently sponsored a workshop entitled "Sleep Insufficiency, Circadian Misalignment, and the Immune Response" (May 16-17, 2019, Rockville, Maryland, USA). Its aim was to highlight basic and clinical advances linking sleep and circadian biology to immune dysfunction, thereby stimulating the application of circadian biology to translational medicine. The Workshop was cosponsored by four NIH institutes-the National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA), National Institute of Allergy and Infectious Diseases (NIAID), and National Institute on Alcohol Abuse and Alcoholism (NIAAA)-reflecting a...

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“…These data suggested that IL-17A might have contributed to viral control in lungs in mice vaccinated with ADJ+GLA. Although IL-17 production is known to be protective against certain fungal and bacterial infections, it is also linked to immune pathology (34,35). In order to evaluate whether vaccine-induced protective immunity in ADJ+GLA mice was associated with lung pathology, we analyzed histopathological changes in lungs after viral challenge (Fig.…”

Section: Adjuvants Regulate Recall T-cell Responses and Protective Hementioning

confidence: 99%

Programming Multifaceted Pulmonary T-Cell Immunity by Combination Adjuvants

Marinaik

Kingstad-Bakke

Lee

et al. 2020

Preprint

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Induction of protective mucosal T-cell memory remains a formidable challenge to vaccinologists. Using a novel adjuvant strategy that elicits unusually potent CD8 and CD4 T-cell responses, we have defined the tenets of vaccine-induced pulmonary T-cell immunity. An acrylic acid-based adjuvant (ADJ), in combination with TLR agonists glucopyranosyl lipid adjuvant (GLA) or CpG promoted mucosal imprinting but engaged distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of TH1/TC1/TH17/TC17 effector/memory T cells. Combination of ADJ with GLA, but not CpG, dampened TCR signaling, mitigated terminal differentiation of effectors and enhanced the development of CD4 and CD8 TRM that protected against H1N1 and H5N1 influenza viruses. Mechanistically, vaccine-elicited CD4 T cells played a vital role in optimal programming of CD8 TRM and anti-viral immunity. Taken together, these findings provide new insights into vaccine-induced multi-faceted mucosal T-cell immunity with significant implications in the development of vaccines against respiratory pathogens.

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Insight Into Non-Pathogenic Th17 Cells in Autoimmune Diseases

Cited by 110 publications

References 74 publications

Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma

Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma

Perfect timing: circadian rhythms, sleep, and immunity — an NIH workshop summary

Programming Multifaceted Pulmonary T-Cell Immunity by Combination Adjuvants

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