Roba M. Talaat
Ashraf A. Tabll
Amira M. Gamal-Eldeen
Remo C. Russo- 1Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City (USC), Sadat City, Egypt
- 2Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, Cairo, Egypt
- 3Egypt Center for Research and Regenerative Medicine, Cairo, Egypt
- 4Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
- 5High Altitude Research Center, Prince Sultan Medical Complex, Al-Hawiyah, Taif University, Taif, Saudi Arabia
- 6Laboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
Editorial on the Research Topic:
Importance of Cytokines and Receptor Members from the IL-1 Family in the Context of Chronic Autoimmune Inflammatory Diseases
The history of the IL-1 cytokine family begins in 1974 with the discovery of the IL-1α and IL-1β, described as two distinct ‘leukocytic pyrogens’, since these proteins promote fever. Today, almost 50 years after its discovery, the IL-1 cytokine family comprises 11 cytokine members encoded by 11 distinct genes in humans and mice (1–4). This family displays a complex regulation that amplify the mechanisms orchestrated by IL-1 members during acute and chronic inflammation (5–7). Recently, evidences have proposed that members of the IL-1 members are closely associated with the abnormal inflammatory and immune responses during chronic autoimmune diseases. Several immunity sensors, evolved to assist host defense by stimulating the IL-1 pathway (2, 5, 6). Regarding the understanding of the IL-1 cytokine family over pasting years, it mainly showed pro-inflammatory activities (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ) but also contained four members that suppress inflammation: two specific receptor antagonists (IL-1Ra and IL-36Ra), and less studied, two members that broadly suppress cytokines and chemokines during innate inflammation (IL-37 and IL-38) (1–8).
This Research Topic cover the recent advances in the role of several IL-1 family members, with particular emphasis on newly discovered IL-36, IL-37, and IL-38, in several autoimmune inflammatory diseases of the skin, gut, and teeth. The authors also discussed the role of cytokine gene polymorphism in disease susceptibility and pathogenesis. With the spread of COVID-19 infection worldwide and the ultimate need for vaccination, the efficacy and safety of COVID-19 vaccination in autoinflammatory rheumatic diseases under immunosuppressive drugs was discussed.
Periodontitis is a chronic inflammatory illness that causes tooth loss by destroying the tooth-supporting tissues (9), and cytokines are involved in periodontitis (10). Liu and Li looked at 147 publications with polymorphisms in 12 interleukins [Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4 and IL-13), Th17 (IL-1α, IL-1β, IL-6, and IL-17), and Treg cytokines (IL-10 and TGF-β). Polymorphisms in the Th2 cytokine family, such as IL-4 and IL-13, have not been linked to periodontitis pathogenesis. However, Th17 cytokine genetic polymorphism may be a risk factor for periodontitis, while Treg cells may have a protective role in preventing periodontal inflammation. In this sense, IL-1 is an important cytokine biomarker in the development and progression of periodontitis.
Chronic inflammatory diseases may emerge in various tissues, including the skin, due to an imbalance in pro-and anti-inflammatory cytokines from the IL-1 family (11–14). Martin et al. summarize the recent advances in the biology of anti-inflammatory members of the IL-1 cytokine family and their roles in controlling inflammatory responses in human and mouse skin. Martin et al. reported that IL-1Ra, IL-36Ra, IL-37, and IL-38, are constitutively expressed in keratinocytes and exert their regulatory roles in skin inflammation, suggesting new ways to treat inflammatory skin diseases.
IL-37, commonly known as IL-1 family member 7 (IL-1F7) (15, 16) show anti-inflammatory properties (17–19), and is considered as a disease biomarker in various inflammatory and autoimmune disorders (20). Santarelli et al. established the first reference range of circulating IL-37 plasma and serum levels in healthy adult humans. Santarelli et al. established a tentative reference range for circulating IL-37 in healthy people. Large, multi-ethnic, healthy population studies are needed to obtain a credible clinical reference range. They also recommended further investigations into demographics, sample matrices, collection, processing, and storage procedures that affect IL-37 detection levels.
With the spread of COVID-19 worldwide, the vaccination is crucial to ending the pandemic and preventing mortality. The immunosuppression established during treatment autoimmune rheumatic diseases (AIIRD) by IL-1 blockage may compromise the immunization process (21, 22). Atagündüz et al. summarize all forms of vaccinations under IL-1 blockade discussing the use and timing of COVID-19 vaccination in patients receiving anti-IL-1 therapy. Atagündüz et al. reported that COVID-19 vaccine efficacy might be lower in patients treated with IL-1 blockade. As noted by Atagündüz et al., COVID-19 develops more rapidly in untreated patients. Atagündüz et al. recommended that patients under IL-1 blockade be vaccinated without interrupting anti-cytokine therapy, especially those patients with ongoing high disease activity, to avoid disease relapses.
As a member of the IL-1 cytokine family, IL-36 cytokines include the anti-inflammatory cytokine IL-36Ra and the pro-inflammatory cytokines IL-36α, IL-36β, and IL-36γ (23). The most of the research has focused on its involvement in autoimmune diseases (24), but have demonstrated in the lung inflammation during infectious and non-infectious disorders (25–27). Peñaloza et al. review the current literature concerning the biology of IL-36 cytokines, including their synthesis and activation, also their impact on myeloid and lymphoid cells during inflammation. They also discussed their function during bacterial and viral lung infections, and other inflammatory lung disorders such as cancer, cystic fibrosis, allergic asthma, chronic obstructive pulmonary disease, and lung fibrosis. Peñaloza et al. also outline recent therapeutic development targeting the IL-36 pathway and the potential to treat lung inflammatory disorders.
The gastrointestinal tract (GIT) is lined by a single cell layer of intestinal epithelial cells (IECs) which are interconnected by the tight junctions (TJs), which serve as a gate or barrier to paracellular permeation of luminal contents (28). Disruption of the intestinal TJ barrier plays an essential role in the pathogenesis of several inflammatory conditions of the gut, including celiac disease and inflammatory bowel disease (IBD), characterized by elevated levels of IL-1 (28–30). In this review, Kaminsky et al. review most of the published studies that deal with the clinical consequences of IL-1β intestinal barrier regulation in intestinal inflammation, the underlying mechanisms and intracellular signaling pathways involved in TJ barrier permeability modulation, and the downstream molecular targets of IL-1β. Kaminsky et al. also discussed the potential therapeutic targeting of the TJ barrier.
In conclusion, this Research Topic highlights recent findings and new insights into the most recent development of the IL-1 family in the pathophysiology of several autoimmune diseases. The current research may provide new insight and advancements for future research targeting IL-1 in autoimmune diseases affecting teeth, skin, and GIT. Finally, in this Research Topic, the authors also go through elements of clinical translation and the biology of cytokines belonging to the IL-1 family in animal models, identifying potential targets for developing novel therapeutic approaches for autoimmunity.
Author Contributions
RT, AT, AG-E and RR performed literature research, discussed the articles, and wrote the manuscript. All authors contributed to the article revision and approved the submitted version.
Funding
This work did not receive financial support for its design and publication. RR is fellow from National Council for Scientific and Technological Development (CNPq) [Grant number: 312839/2020-0], and the laboratory is supported by grant from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Rede Mineira de Pesquisa Translacional em Imunobiológicos e Biofármacos no Câncer (REMITRIBIC) [Grant number: RED-00031-21] and Demanda Universal 01/2021 [Grant number: APQ-02571-21].
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s Note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev (2018) 281(1):8–27. doi: 10.1111/imr.12621
2. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family”. Annu Rev Immunol (2009) 27:519–50. doi: 10.1146/annurev.immunol.021908.132612
3. Boraschi D, Italiani P, Weil S, Martin MU. The family of the interleukin-1 receptors. Immunol Rev (2018) 281(1):197–232. doi: 10.1111/imr.12606
4. Dinarello CA. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat Rev Rheumatol (2019) 15(10):612–32. doi: 10.1038/s41584-019-0277-8
5. Netea MG, van de Veerdonk FL, van der Meer JW, Dinarello CA, Joosten LA. Inflammasome-independent regulation of IL-1-family cytokines. Annu Rev Immunol (2015) 33:49–77. doi: 10.1146/annurev-immunol-032414-112306
6. Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity (2013) 39(6):1003–18. doi: 10.1016/j.immuni.2013.11.010
7. Weber A, Wasiliew P, Kracht M. Interleukin-1 (IL-1) pathway. Sci Signal (2010) 3(105):cm1. doi: 10.1126/scisignal.3105cm1
8. Cavalli G, Dinarello CA. Suppression of inflammation and acquired immunity by IL-37. Immunol Rev (2018) 281(1):179–90. doi: 10.1111/imr.12605
9. Pacheco CMF, Maltos KLM, Shehabeldin MS, Thomas LL, Zhuang Z, Yoshizawa S, et al. Local sustained delivery of anti-IL-17a antibodies limits inflammatory bone loss in murine experimental periodontitis. J Immunol (2021) 206:2386–92. doi: 10.4049/jimmunol.2001432
10. Plemmenos G, Evangeliou E, Polizogopoulos N, Chalazias A, Deligianni M, Piperi C. Central regulatory role of cytokines in periodontitis and targeting options. Curr Med Chem (2021) 28(15):3032–58. doi: 10.2174/0929867327666200824112732
11. Pasparakis M, Haase I, Nestle FO. Mechanisms regulating skin immunity and inflammation. Nat Rev Immunol (2014) 14:289–301. doi: 10.1038/nri3646
13. Tsang MS, Sun X, Wong CK. The role of new IL-1 family members (IL-36 and IL-38) in atopic dermatitis, allergic asthma, and allergic rhinitis. Curr Allergy Asthma Rep (2020) 20:840. doi: 10.1007/s11882-020-00937-1
14. Conti P, Pregliasco FE, Bellomo RG, Gallenga CE, Caraffa A, Kritas SK, et al. Mast cell cytokines IL-1, IL-33, and IL-36 mediate skin inflammation in psoriasis: A novel therapeutic approach with the anti-inflammatory cytokines IL-37, IL-38, and IL-1Ra. Int J Mol Sci (2021) 22:15 8076. doi: 10.3390/ijms22158076
15. Kumar S, McDonnell PC, Lehr R, Tierney L, Tzimas MN, Griswold DE, et al. Identification and initial characterization of four novel members of the interleukin-1 family. J Biol Chem (2000), Apr 7; 275(14):10308–14. doi: 10.1074/jbc.275.14.10308
16. Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA. IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol (2010), Nov; 11(11):1014–22. doi: 10.1038/ni.1944
17. Dinarello CA, Nold-Petry C, Nold M, Fujita M, Li S, Kim S, et al. Suppression of innate inflammation and immunity by interleukin-37. Eur J Immunol (2016) 46(5):1067–81. doi: 10.1002/eji.201545828
18. Li S, Amo-Aparicio J, Neff CP, Tengesdal IW, Azam T, Palmer BE, et al. Role for nuclear interleukin-37 in the suppression of innate immunity. Proc Natl Acad Sci USA (2019) 116:4456–61. doi: 10.1073/pnas.1821111116
19. Monastero RN, Pentyala S. Cytokines as biomarkers and their respective clinical cutoff levels. Int J Inflam (2017) 2017:4309485. doi: 10.1155/2017/4309485
20. Soy M, Keser G, Atagunduz P, Mutlu MY, Gunduz A, Koybaşi G, et al. A practical approach for vaccinations including COVID-19 in autoimmune/ autoinflammatory rheumatic diseases: A non-systematic review. Clin Rheumatol (2021) 40(9):3533–45. doi: 10.1007/s10067-021-05700-z
21. Lopez Bernal J, Andrews N, Gower C, Robertson C, Stowe J, Tessier E, et al. Effectiveness of the pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: Test negative case-control study. BMJ (2021) 13(373):n1088. doi: 10.1136/bmj.n1088
22. Curtis JR, Johnson SR, Anthony DD, Arasaratnam RJ, Baden LR, Bass AR, et al. American College of rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases –version 2. Arthritis Rheumatol (2021) 73(8):e30–45. doi: 10.1002/art.41877
23. Kovach MA, Singer BH, Newstead MW, Zeng X, Moore TA, White ES, et al. IL-36gamma is secreted in microparticles and exosomes by lung macrophages in response to bacteria and bacterial components. J Leukoc Biol (2016) 100(2):413–21. doi: 10.1189/jlb.4A0315-087R
24. Chen WJ, Yu X, Yuan XR, Chen BJ, Cai N, Zeng S, et al. The role of IL-36 in the pathophysiological processes of autoimmune diseases. Front Pharmacol (2021) 12:727956. doi: 10.3389/fphar.2021.727956
25. Aoyagi T, Newstead MW, Zeng X, Nanjo Y, Peters-Golden M, Kaku M, et al. Interleukin-36gamma and IL-36 receptor signaling mediate impaired host immunity and lung injury in cytotoxic pseudomonas aeruginosa pulmonary infection: Role of prostaglandin E2. PloS Pathog (2017) 13(11):e1006737. doi: 10.1371/journal.ppat.1006737
26. Liu XG, Li J, Zheng LJ, Han B, Huang F. Interleukin-36 receptor antagonist alleviates airway inflammation in asthma via inhibiting the activation of interleukin-36 pathway. Int Immunopharmacol (2020) 81:106200. doi: 10.1016/j.intimp.2020.106200
27. Peñaloza HF, Olonisakin TF, Bain WG, Qu Y, van der Geest R, Zupetic J, et al. Thrombospondin-1 restricts interleukin-36gamma-Mediated neutrophilic inflammation during pseudomonas aeruginosa pulmonary infection. mBio (2021) 12(2):e03336-20. doi: 10.1128/mBio.03336-20
28. Ma TY, Nighot P, Al-Sadi R. Tight junctions and the intestinal barrier. In: Physiology of the gastrointestinal tract: Sixth edition. London, United Kingdom, San Diego, CA, United States, Cambridge, MA, United States, K idlington, United Kingdom: Elsevier Inc (2018). p. 587–639.
29. Bhatia AM, Stoll BJ, Cismowski MJ, Hamrick SE. Cytokine levels in the preterm infant with neonatal intestinal injury. Am J Perinatol (2014) 31(6):489–96. doi: 10.1055/s-0033-1353437
Keywords: IL-1, chronic inflammation, autoimmunity, COVID-19, periodontitis
Citation: Talaat RM, Tabll AA, Gamal-Eldeen AM and Russo RC (2022) Editorial: Importance of cytokines and receptor members from the IL-1 family in the context of chronic autoimmune inflammatory diseases. Front. Immunol. 13:974261. doi: 10.3389/fimmu.2022.974261
Received: 21 June 2022; Accepted: 04 July 2022;
Published: 19 July 2022.
Edited and Reviewed by:
Silvano Sozzani, Sapienza University of Rome, ItalyCopyright © 2022 Talaat, Tabll, Gamal-Eldeen and Russo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Roba M. Talaat, roba.talaat@gebri.usc.edu.eg; Remo C. Russo, remo@ufmg.br