The role of IL-12/23 in T cell–related chronic inflammation: implications of immunodeficiency and therapeutic blockade

Schurich, Anna; Raine, Charles; Morris, Vanessa; Ciurtin, Coziana

doi:10.1093/rheumatology/kex186

Cited by 42 publications

(26 citation statements)

References 73 publications

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“…A decrease in bacterial diversity and levels of IgA along with increased dysbiosis were observed in common variable immune deficiency (CVID) patients (Jørgensen et al, 2016). Dysbiosis in the gut microbiota was also present in other immunodeficiencies such as those involving interleukin-10, -17, or -23 (Cua and Tato, 2010; Godinez et al, 2011; Nagalingam et al, 2013; Schurich et al, 2017), nucleotide-binding oligomerization domain (NOD)-like receptors (NLR) (Frank et al, 2011; Rehman et al, 2011; Arai et al, 2015; Hu et al, 2018), or toll-like receptors (Carvalho et al, 2012; Ubeda et al, 2012), and the susceptibility to colitis observed in the corresponding immunodeficient mice showed a clear dependence upon the composition of the microbiome.…”

Section: Discussionmentioning

confidence: 99%

Immunodeficiency Promotes Adaptive Alterations of Host Gut Microbiome: An Observational Metagenomic Study in Mice

et al. 2019

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The crosstalk between the gut microbiota and immune state of the host is an essential focus in academia and clinics. To explore the dynamic role of the microbiota in response to immune deficiency, we comprehensively assessed the microbiome of 90 mouse fecal samples, across three time points including two immunodeficiency models, namely severe combined immunodeficient (SCID) mice and non-obese diabetic SCID (NOD/SCID) mice, with BALB/cA as a control strain. Metagenomic analysis revealed a decrease in alpha diversity and the existence of a clear structural separation in the microbiota of immunodeficient mice. Although nuances exist between SCID and NOD/SCID mice, an increase in the protective microbiota, in particular Lactobacillus, contributed the most to the discrimination of immunodeficient and control mice. Further data regarding the red blood cell (RBC) concentration and serum IgA level during different stages of development support the concept of the microbiota alleviating the advancement of immune deficiency, which is called microbial compensation. Taken together, these results demonstrate the dynamic impact of immunodeficiency on the gut microbiota and the adaptive alteration of the microbiota that may influence the host state.

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Section: Discussionmentioning

confidence: 99%

Immunodeficiency Promotes Adaptive Alterations of Host Gut Microbiome: An Observational Metagenomic Study in Mice

et al. 2019

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“…It is now known that the production of this cytokine by dendritic cells and macrophages can be stimulated by exposure to bacteria and the involvement of Toll‐like receptors, and that the consequent production and response of IL‐17 are important in neutralizing infectious organisms 54 . Also, a genetic deficiency of the p40 subunit shared by IL‐12 and IL‐23 has been linked to increased susceptibility and severity of Salmonella or mycobacterial infection 55 …”

Section: Reactivation Of Tuberculosis With Il‐17 and Il‐23 Inhibitorsmentioning

confidence: 99%

Risk of tuberculosis reactivation with interleukin (IL)‐17 and IL‐23 inhibitors in psoriasis – time for a paradigm change

Nogueira

Warren

Torres

2020

Acad Dermatol Venereol

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Tuberculosis is an infectious disease with a major global impact, ranked in the top 10 mortality causes worldwide. In an immunocompetent individual, the host defence mechanisms control Mycobacterium tuberculosis infection and induce the latent form of the disease. However, in the presence of diseases or therapies, which exert an immunosuppressive effect, latent tuberculosis can be re‐activated. Psoriasis is an immune‐mediated, inflammatory disease, and its treatment has rapidly evolved over the last few years. It has long been recognized that the tumour necrosis factor (TNF)‐α inhibitors are associated with increased risk of reactivation of latent tuberculosis infection. Thus, international guidelines have been suggesting tuberculosis screening before starting the treatment with all biological agents since then. In addition, the institution of chemoprophylaxis in the presence of latent tuberculosis and the annual screening for tuberculosis thereafter have also been indicated. However, anti‐tuberculosis treatments can have significant side‐effects and there are currently several contraindications to their use. The risk benefit of starting anti‐tuberculous treatment should be carefully weighed up. The emergence of new biological drugs for the treatment of psoriasis, such as interleukin (IL)‐17 and IL‐23 inhibitors, has reignited the subject of tuberculosis reactivation as it is possible that IL‐17 and 23 blockade do not carry the same risk of TB reactivation as TNF‐α inhibitors. Although preclinical studies have shown that cytokines IL‐17 and IL‐23 have a possible role against infection with M. tuberculosis, data from clinical trials and post‐marketing surveillance with drugs that inhibit these cytokines appear to suggest that they are not crucial to this response. In this article, we review the available data on tuberculosis reactivation after the treatment of psoriasis with IL‐17 and IL‐23 inhibitors, and its possible impact on the way we currently manage latent tuberculosis infection before or after starting treatment with these new drugs.

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“…IL‐38 suppresses inflammation by inhibiting the production of IL‐1β and other IL‐family members in patients with SARS‐CoV‐2 108 . In contrast, activated B cells induce IL‐12 release in patients with SARS‐CoV‐2, stimulating the growth and activity of T and NK cells, and further inducing the production of proinflammatory cytokines 78,90 . Hence, the blocking of IL‐12, and the administration of IL‐38 offers a novel therapeutic strategy against SARS‐CoV‐2 infection.…”

Section: Immunity‐induced Inflammation During Sars‐cov‐2 Infectionmentioning

confidence: 99%

SARS‐CoV‐2‐mediated immune system activation and potential application in immunotherapy

Tan

Tang

2020

Medicinal Research Reviews

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Although novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐mediated pulmonary inflammation has recently attracted great attention, its pathology and pathogenesis are not clear. Notably, due to both its high infective and pathogenicity, SARS‐CoV‐2 infection may cause a severe sometimes fatal respiratory disease. A specific vaccine, which relies on the analysis of SARS‐CoV‐2 structural protein‐derived antigenic peptides, is indispensable for restraining the spread and reducing the mortality of SARS‐CoV‐2. SARS‐CoV‐2 infections activate cytototxic, myeloid‐derived suppressor cells, dendritic cells, macrophages, as well as natural killer, B, helper T, and regulatory T cells, thus further stimulating innate and antigen‐specific immune responses. Nevertheless, many immune effector cells cause hyperinflammation and pulmonary immunopathology by releasing proinflammatory cytokines and chemokines, including interferon (IFN)‐α, IFN‐β, IFN‐γ, monocyte chemoattractant protein‐1, macrophage inflammatory protein (MIP)‐1A, MIP1B, interleukin (IL)‐1, IL‐2, IL‐4, IL‐6, IL‐7, IL‐8, IL‐9, IL‐12, IL‐17, and IL‐18, platelet‐derived growth factor, fibroblast growth factor, tumor necrosis factor‐α, and induced protein 10. Interestingly, related products derived from SARS‐CoV‐2 are likely to trigger immune evasion. Therefore, investigating SARS‐CoV‐2‐specific vaccines, blocking immunopathology, and prohibiting immune evasion are urgently required for treating SARS‐CoV‐2 infection. In this review, we emphatically illuminated the development of a SARS‐CoV‐2‐specific vaccine based on the analysis of epitopes, also expounding the molecular mechanisms of SARS‐CoV‐2‐mediated cytokine release syndrome. Furthermore, we comprehensively discussed SARS‐CoV‐2‐associated immune evasion and lung immunopathology. Lastly, potential therapeutic strategies against SARS‐CoV‐2 were explored.

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The role of IL-12/23 in T cell–related chronic inflammation: implications of immunodeficiency and therapeutic blockade

Cited by 42 publications

References 73 publications

Immunodeficiency Promotes Adaptive Alterations of Host Gut Microbiome: An Observational Metagenomic Study in Mice

Immunodeficiency Promotes Adaptive Alterations of Host Gut Microbiome: An Observational Metagenomic Study in Mice

Risk of tuberculosis reactivation with interleukin (IL)‐17 and IL‐23 inhibitors in psoriasis – time for a paradigm change

SARS‐CoV‐2‐mediated immune system activation and potential application in immunotherapy

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