Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis

Ito, Takashi; Tanaka, Toshihiro; Nakamaru, Koh; Tomiyama, Takashi; Yamaguchi, Takashi; Ando, Yugo; Ikeura, Tsukasa; Fukui, Toshiro; Uchida, Kazushige; Nishio, Akiyoshi; Okazaki, Kazuichi

doi:10.1007/s00535-020-01689-5

Cited by 15 publications

(9 citation statements)

References 42 publications

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“…IL-27 is primarily secreted by activated macrophages and dendritic cells. [91][92][93] Binding of IL-27 to its receptor Il-27R and gp130 leads to activation of STAT1 and inhibits GATA-3 which further downregulates IL-4 and reduces mucin production via MUC5AC.…”

Section: Anti-inflammatory Role Of Il-27mentioning

confidence: 99%

Cytokine Storm and Mucus Hypersecretion in COVID-19: Review of Mechanisms

Khan¹,

Khan²,

Munier³

et al. 2021

JIR

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Mucus is an integral part of the respiratory physiology. It protects the respiratory tract by acting as a physical barrier against inhaled particles and microbes. Excessive inflammation in conditions such as COVID-19 can result in over-production of mucus which obstructs the airway. Build-up of mucus can also contribute to recurrent airway infection, causing further obstruction. This article summarizes the current understanding and knowledge of respiratory mucus production and proposes the role of cytokine storm in inducing sudden mucus hypersecretion in COVID-19. Based on these cascades, the active constituents that inhibit or activate several potential targets are outlined for further research. These may be explored for the discovery and design of drugs to combat cytokine storm and its ensuing complications.

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Section: Anti-inflammatory Role Of Il-27mentioning

confidence: 99%

Cytokine Storm and Mucus Hypersecretion in COVID-19: Review of Mechanisms

Khan¹,

Khan²,

Munier³

et al. 2021

JIR

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“…IL-35: This cytokine is a heterodimeric member of the IL-12 family (IL-12, IL-23, IL-27) ( 65 ). Several anti-inflammatory effects of IL-35 have been reported: induction of CD4 + CD25 + Tregs proliferation, IL-10 and TGF- β secretion, suppression of CD4 + CD25 − effector cells proliferation, and inhibition of Th17 differentiation ( 66 , 67 ). Nonetheless, many research have indicated that IL-35 mediates immune suppression in mouse model but have limited effectiveness in humans ( 68 , 69 ).…”

Section: Suppressive Mechanismsmentioning

confidence: 99%

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

et al. 2021

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Regulatory T cells (Tregs) are an immunosuppressive subgroup of CD4+ T cells which are identified by the expression of forkhead box protein P3 (Foxp3). The modulation capacity of these immune cells holds an important role in both transplantation and the development of autoimmune diseases. These cells are the main mediators of self-tolerance and are essential for avoiding excessive immune reactions. Tregs play a key role in the induction of peripheral tolerance that can prevent autoimmunity, by protecting self-reactive lymphocytes from the immune reaction. In contrast to autoimmune responses, tumor cells exploit Tregs in order to prevent immune cell recognition and anti-tumor immune response during the carcinogenesis process. Recently, numerous studies have focused on unraveling the biological functions and principles of Tregs and their primary suppressive mechanisms. Due to the promising and outstanding results, Tregs have been widely investigated as an alternative tool in preventing graft rejection and treating autoimmune diseases. On the other hand, targeting Tregs for the purpose of improving cancer immunotherapy is being intensively evaluated as a desirable and effective method. The purpose of this review is to point out the characteristic function and therapeutic potential of Tregs in regulatory immune mechanisms in transplantation tolerance, autoimmune diseases, cancer therapy, and also to discuss that how the manipulation of these mechanisms may increase the therapeutic options.

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“…Among the 5123 identified records, 234 full-text articles were assessed for eligibility and 92 studies were included in the qualitative synthesis [ 3 , 6 , 7 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , …”

Section: Resultsmentioning

confidence: 99%

“…Meanwhile, Tregs maintain continued immune tolerance and prevent immunological reactions by releasing IL-35. Ito et al [ 43 ] identified Treg anti-inflammatory activity through elevated plasma IL-35 and tissue IL-35 subunit expression in patients with type 1 AIP. Supplemental Table S6 includes studies that investigate cytokines in AIP.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review

Dugic

Gil

Mellenthin³

et al. 2022

Biomedicines

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Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.

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Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis

Cited by 15 publications

References 42 publications

Cytokine Storm and Mucus Hypersecretion in COVID-19: Review of Mechanisms

Cytokine Storm and Mucus Hypersecretion in COVID-19: Review of Mechanisms

The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review

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