1-Minute Summary: Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation

Expert Name
Haiyu Hong
Expert Affiliation
Department of Otolaryngology, Allergy Center, The Fifth Affiliated Hospital of Sun Yat‐sen University, Zhuhai, China
Journal
European Journal of Allergy and Clinical Immunology

The concept of united airway diseases (UAD) includes allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, all of which share common immune-pathogenic mechanisms [1-4]. Moreover, a systemic link between upper and lower airways exists by shared molecular and inflammatory mechanisms, including overproduction of type-2 cytokines in AR, CRS, and asthma [5,6], not limited to the target organs.

There is a hypothesis that emphasizes IL-25, IL-33, and TSLP as key regulatory factors that link epithelial-mesenchymal communications and induce pathophysiological changes in the airway [1].

IL-25 is a Th2 cell-derived pro-inflammatory cytokine and a member of the IL-17 family [7]. It is rapidly released upon exposure to allergens containing protease activities, inducing allergic inflammation [8]. IL-25 has numerous responders and mediates both the innate and adaptive immune system to evoke a Th2-skewed mucosal inflammation [1].

IL-33 is a member of the IL-1 family and induces Th2 inflammation in a manner similar to IL-25 [9-11]. In the lower airway, the distinct increase in IL-33 is responsible for the development and exacerbation of airway hypersensitivity and asthma [12,13]. Moreover, IL-33 can play a role in allergic inflammation. The pathways and mechanisms of IL-33–induced airway allergy still remain ambiguous [1].

TSLP was first identified as a IL-7–like growth factor and is localized in epithelial cells, mast cells, bronchial smooth muscle cells, dendritic cells, and fibroblasts in the airway [15,16]. Endogenous triggers include pro-inflammatory cytokines, Th2-related cytokines, and IgE [16]. Upon endogenous and exogenous triggers, TSLP can exacerbate allergic inflammation via activating downstream responders, among others Th2 cells and myeloid dendritic cells [17]. TSLP is involved in the pathogenesis of inflammatory airway diseases including AR, CRS, asthma, and COPD [18].

Reciprocal interactions of IL-25, IL-33, TSLP, and other cytokines make up a complex regulatory network. They can induce type-2 responses and their synergy can further exacerbate induced inflammation. However, IL-17A, IL-1β, INFγ, and TGFβ can suppress the expression of these epithelium-derived cytokines, thus inhibiting type-2 responses (see Figure) [20-22].

hypersensitivity and asthma [12,13]. Moreover, IL-33 can play a role in allergic inflammation. The pathways and mechanisms of IL-33–induced airway allergy still remain ambiguous [1].

TSLP was first identified as a IL-7–like growth factor and is localized in epithelial cells, mast cells, bronchial smooth muscle cells, dendritic cells, and fibroblasts in the airway [15,16]. Endogenous triggers include pro-inflammatory cytokines, Th2-related cytokines, and IgE [16]. Upon endogenous and exogenous triggers, TSLP can exacerbate allergic inflammation via activating downstream responders, among others Th2 cells and myeloid dendritic cells [17]. TSLP is involved in the pathogenesis of inflammatory airway diseases including AR, CRS, asthma, and COPD [18].

Reciprocal interactions of IL-25, IL-33, TSLP, and other cytokines make up a complex regulatory network. They can induce type-2 responses and their synergy can further exacerbate induced inflammation. However, IL-17A, IL-1β, INFγ, and TGFβ can suppress the expression of these epithelium-derived cytokines, thus inhibiting type-2 responses (see Figure) [20-22].

Figure: Cytokine network and their reciprocal regulation [1]

In conclusion, TSLP, IL-25, and IL-33 are produced as the first line of defense against infections and stimulations in the airway epithelium, thus leading to potent augmentations of allergic inflammations and exerting effects as “bridges” linking innate and adaptive airway mucosal immunities [1].

 

References

  1. Hong H, Liao S, Chen F, Yang Q, Wang DY. Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type-2 inflammation [published online ahead of print, 2020 Aug 1]. Allergy. 2020;10.1111/all.14526.
  2. Pfaar O, Agache I, Blay F, et al. Perspectives in allergen immunotherapy: 2019 and beyond. Allergy. 2019;74(Suppl 108):3-25.
  3. Yii A, Tay TR, Choo XN, Koh M, Tee A, Wang DY. Precision medicine in united airways disease: A “treatable traits” approach. Allergy. 2018;73(10):1964-1978.
  4. Samitas K, Carter A, Kariyawasam HH, Xanthou G. Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited. Allergy. 2018;73(5):993-1002.
  5. Campo P, Eguiluz-Gracia I, Plaza-Serón MC, et al. Bronchial asthma triggered by house dust mites in patients with local allergic rhinitis. Allergy. 2019;74(8):1502-1510.
  6. Rondon C, Campo P, Eguiluz-Gracia I, et al. Local allergic rhinitis is an independent rhinitis phenotype: The results of a 10-year follow-up study. Allergy. 2018;73(2):470-478.
  7. Fort MM, Cheung J, Yen D, et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2001;15(6):985-995.
  8. Kouzaki H, Tojima I, Kita H, Shimizu T. Transcription of interleukin-25 ind extracellular release of the protein is regulated by allergen proteases in airway epithelial cells. Am J Respir Cell Mol Biol. 2013;49(5):741-750.
  9. Ihara F, Sakurai D, Yonekura S, et al. Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy. Allergy. 2018;73(9):1823-1832.
  10. Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23(5):479-490.
  11. Zhou X, Wei T, Cox CW, Jiang Y, Roche WR, Walls AF. Mast cell chymase impairs bronchial epithelium integrity by degrading cell junction molecules of epithelial cells. Allergy. 2019;74(7):1266-1276.
  12. Hesse L, van Ieperen N, Habraken C, et al. Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model. Allergy. 2018;73(4):862-874.
  13. Kaur D, Gomez E, Doe C, et al. IL-33 drives airway hyper-responsiveness through IL-13-mediated mast cell: airway smooth muscle crosstalk. Allergy. 2015;70(5):556-567.
  14. Kim EH, Kim JH, Samivel R, et al. Intralymphatic treatment of flagellin-ovalbumin mixture reduced allergic inflammation in murine model of allergic rhinitis. Allergy. 2016;71(5):629-639.
  15. Chen X, Deng R, Chi W, et al. IL-27 signaling deficiency develops Th17-enhanced Th2-dominant inflammation in murine allergic conjunctivitis model. Allergy. 2019;74(5):910-921.
  16. Takai T. TSLP expression: cellular sources, triggers, and regulatory mechanisms. Allergol Int. 2012;61(1):3-17.
  17. Maruyama N, Takai T, Kamijo S, et al. Cyclooxygenase inhibition in mice heightens adaptive- and innate-type responses against inhaled protease allergen and IL-33. Allergy. 2019;74(11):2237-2240.
  18. Chen Z-G, Zhang T-T, Li H-T, et al. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite. PLoS One. 2013;8(1):e51268.
  19. Liao B, Cao P-P, Zeng M, et al. Interaction of thymic stromal lymphopoietin, IL-33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps. Allergy. 2015;70(9):1169-1180.
  20. Xu G, Zhang L, Wang DY, et al. Opposing roles of IL-17A and IL-25 in the regulation of TSLP production in human nasal epithelial cells. Allergy. 2010;65(5):581-589.
  21. Ogasawara N, Klingler AI, Tan BK, et al. Epithelial activators of type 2 inflammation: Elevation of thymic stromal lymphopoietin, but not IL-25 or IL-33, in chronic rhinosinusitis with nasal polyps in Chicago, Illinois. Allergy. 2018;73(11):2251-2254.
  22. Tan H-T, Hagner S, Ruchti F, et al. Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice. Allergy. 2019;74(2):294-307.

 

62 thoughts

  2. The rising popularity of dolls that sex is a fantastic option to satisfy your Sexual Doll desires.
    They are made of soft silicone, but solid and safe to handle.
    Modern sex toys have no flavor and are easy to wash.

  4. European Sex Dolls have become a popular way
    to fulfill your sexual desires. They are highly
    realistic and come in various sizes, eye colors, and hairstyles.
    A majority of these European love dolls are available with different sex
    scenes.

    My web-site … sexdoll

  7. Posing your curvy sex toys can make them more attractive.
    You can have your doll have straight breasts or a curly back, or both.

    They look real and will draw potential owners who appreciate their dimensions.

    Feel free to surf to my blog post – sexdolls (Peatix.com)

  8. Totobet HK is an online site that lets players
    play the 4D lottery game. This website has several thousand figures and is thought to
    be the most popular totobet lottery game in the world.

  10. Asian Real Sex dolls dolls are
    a popular toy for erotic pleasure for women and men. These erotic dolls are made with
    high-end TPE materials and are equipped with various characteristics that be a great option for satisfying any sexual urge.

  12. When you play togel hongkong, make sure you know the details of the betul latar belakang hk hari ini.
    The information you need to know is vital if you are hoping to be a winner.
    The data that you need is the keuntungan maximum in the
    Pengeluaran hk
    pool.

  13. Although silicone has long been the most coveted of sex dolls, TPE has recently emerged as a
    dark horse that is providing a tough competition for silicone-based sex toys.

    my web page Sexual Doll

  14. Betting online offers bettors as well as bookmakers many advantages.
    Betting on online sites allows people to bet on their favourite sports and can also
    make them money. These sites provide a variety of ways to deposit funds.

    Feel free to visit my homepage … Gaming (Heeraispat.Com)

  18. The first agency that deals with European sexual dolls is
    located in Barcelona, Spain. The company boasts four working girls,
    and boasts that its customers cannot tell the difference between the real woman and a sex model.

    Here is my webpage: sexdoll cheap

  19. A Male Sex Doll is a ideal gift for a variety of reasons.

    Sex dolls are ideal for a gift to give your partner or
    girlfriend. These toys will make your partner feel happy.

    Review my blog – sexdoll sale

  22. Although silicone has long been the undisputed king of sex dolls TPE has
    recently been recognized as an unknown horse offering a formidable challenge to silicone-based sexual toys.

    my blog realsexdoll

  24. There are many reasons to engage in betting on sports (Jk-sun.Com), from the possibility of making profits to the fact that it brings
    excitement and something to be a part of to the overall experience.

  27. Asian Japanese sex dolls make the sex experience more realistic and enjoyable for both genders.
    They’re a low-cost and easy alternative to real life
    partners. They can fulfill the sexual Doll fantasies and
    be faithful companions.

  28. Gambling online has gained popularity over the last decade.
    In 1996, there were only fifteen websites. In 1997
    there were more than 200 websites. In 1998, a Frost & Sullivan report stated that online gambling brought in $830 million in revenue.

    my web-site … bet (rockypreps.com)

  29. There are many benefits when you play at an online casino.
    It isn’t necessary to shell out a large amount of money.
    Many online casinos provide free games, and players can test them
    out to determine what games they like the best.

    Also visit my site; slots (Naotoogata.com)

  30. There are a myriad of treatment options for gambling addiction. One-on-one
    counseling or medication, lifestyle changes, and medication are
    all alternatives. This can turn into an addiction if you are unable to resist engaging in it.

    My blog gambler; hadistore.Com,

  32. The increasing popularity of sex dolls is a great option to satisfy your sexual fantasies.
    While they’re made from soft silicone, they’re very solid inside and are safe to touch.
    The latest sex toys are free of taste and are simple to clean.

    My page; sexdoll for men

  33. It is possible to make curvy dolls sexier by posing them.
    You can decide to dress your doll’s breasts straight either curved in the back or
    both. These sex toys look very real and are sure to attract future
    owners who love their size.

    my page :: sexdoll sale

  35. Asian Japanese sex dolls make the sex experience more
    realistic and enjoyable for both women and men. They provide a practical
    and inexpensive alternative to actual lovers.

    Feel free to surf to my website; Sexual Doll

  47. We are a group of volunteers and opening a new scheme in our community. Your site provided us with valuable info to work on. Youve done an impressive job and our entire community will be thankful to you.

Leave a Reply

Your email address will not be published.