Update on Type 2 Immunity

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2024 Nov 11

PMID 39528097

Authors

Magdalena M Gorska

Affiliations

Soon will be listed here.

Abstract

This review article summarizes and comments on the mechanistic work on type 2 immunity published between January 2022 and September 2024. Type 2 immunity is characterized by the production of IL-4, IL-5, IL-9, and IL-13 and is primarily known for its detrimental roles in allergic diseases and its protective roles in helminth infections. Other functions of type 2 immunity include protection against venoms and toxins, wound healing, tissue remodeling, regeneration, and metabolic homeostasis. This review article discusses novel findings on regulation of these processes and disease states by select cells and humoral factors of type 2 immunity, including group 2 innate lymphoid cells, CD4 T cells, mast cells, peripheral neurons, and IgE. The article also describes novel discoveries on regulation of these factors and cells by environmental exposures and the host. Further, the article discusses select genetic mouse models that were developed recently and have the potential to accelerate the field. Finally, the article comments on the significance of novel discoveries to clinical medicine, including drug development.

References

Gruber C, Calis J, Buta S, Evrony G, Martin J, Uhl S . Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 Kinase Transcriptional and Biochemical Function. Immunity. 2020; 53(3):672-684.e11. PMC: 7398039. DOI: 10.1016/j.immuni.2020.07.006. View

Helou D, Shafiei-Jahani P, Hurrell B, Painter J, Quach C, Howard E . LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity. J Allergy Clin Immunol. 2021; 149(1):223-236.e6. PMC: 8674385. DOI: 10.1016/j.jaci.2021.05.042. View

Monticelli L, Sonnenberg G, Abt M, Alenghat T, Ziegler C, Doering T . Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol. 2011; 12(11):1045-54. PMC: 3320042. DOI: 10.1031/ni.2131. View

Michieletto M, Tello-Cajiao J, Mowel W, Chandra A, Yoon S, Joannas L . Multiscale 3D genome organization underlies ILC2 ontogenesis and allergic airway inflammation. Nat Immunol. 2022; 24(1):42-54. PMC: 10134076. DOI: 10.1038/s41590-022-01295-y. View

Badrani J, Strohm A, Lacasa L, Civello B, Cavagnero K, Haung Y . RNA-binding protein RBM3 intrinsically suppresses lung innate lymphoid cell activation and inflammation partially through CysLT1R. Nat Commun. 2022; 13(1):4435. PMC: 9338970. DOI: 10.1038/s41467-022-32176-5. View

Zou D, Yin Z, Yi S, Wang G, Guo Y, Xiao X . CD4 T cell immunity is dependent on an intrinsic stem-like program. Nat Immunol. 2024; 25(1):66-76. PMC: 11064861. DOI: 10.1038/s41590-023-01682-z. View

Klose C, Mahlakoiv T, Moeller J, Rankin L, Flamar A, Kabata H . The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation. Nature. 2017; 549(7671):282-286. PMC: 6066372. DOI: 10.1038/nature23676. View

Neill D, Wong S, Bellosi A, Flynn R, Daly M, Langford T . Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010; 464(7293):1367-70. PMC: 2862165. DOI: 10.1038/nature08900. View

Hayes M, Ward S, Crawford G, Castro Seoane R, Jackson W, Kipling D . Inflammation-induced IgE promotes epithelial hyperplasia and tumour growth. Elife. 2020; 9. PMC: 6959995. DOI: 10.7554/eLife.51862. View

10.

Fukue Y, Sato T, Teranishi H, Hanada R, Takahashi T, Nakashima Y . Regulation of gonadotropin secretion and puberty onset by neuromedin U. FEBS Lett. 2006; 580(14):3485-8. DOI: 10.1016/j.febslet.2006.05.025. View

11.

Flayer C, Kernin I, Matatia P, Zeng X, Yarmolinsky D, Han C . A γδ T cell-IL-3 axis controls allergic responses through sensory neurons. Nature. 2024; 634(8033):440-446. DOI: 10.1038/s41586-024-07869-0. View

12.

Del Bel K, Ragotte R, Saferali A, Lee S, Vercauteren S, Mostafavi S . JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome. J Allergy Clin Immunol. 2017; 139(6):2016-2020.e5. DOI: 10.1016/j.jaci.2016.12.957. View

13.

Alhallak K, Nagai J, Zaleski K, Marshall S, Salloum T, Derakhshan T . Mast cells control lung type 2 inflammation via prostaglandin E-driven soluble ST2. Immunity. 2024; 57(6):1274-1288.e6. PMC: 11168874. DOI: 10.1016/j.immuni.2024.05.003. View

14.

Trier A, Ver Heul A, Fredman A, Le V, Wang Z, Auyeung K . IL-33 potentiates histaminergic itch. J Allergy Clin Immunol. 2023; 153(3):852-859.e3. PMC: 10939899. DOI: 10.1016/j.jaci.2023.08.038. View

15.

Christianson C, Goplen N, Zafar I, Irvin C, Good Jr J, Rollins D . Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33. J Allergy Clin Immunol. 2015; 136(1):59-68.e14. PMC: 4494983. DOI: 10.1016/j.jaci.2014.11.037. View

16.

Blanquart E, Mandonnet A, Mars M, Cenac C, Anesi N, Mercier P . Targeting androgen signaling in ILC2s protects from IL-33-driven lung inflammation, independently of KLRG1. J Allergy Clin Immunol. 2021; 149(1):237-251.e12. DOI: 10.1016/j.jaci.2021.04.029. View

17.

Szeto A, Clark P, Ferreira A, Heycock M, Griffiths E, Jou E . Mef2d potentiates type-2 immune responses and allergic lung inflammation. Science. 2024; 384(6703):eadl0370. PMC: 7616247. DOI: 10.1126/science.adl0370. View

18.

Usui K, Nakashima C, Takahashi S, Okada T, Ishida Y, Nakajima S . TRPV1-positive sensory nerves and neuropeptides are involved in epidermal barrier repair after tape stripping in mice. J Allergy Clin Immunol. 2023; 153(3):868-873.e4. DOI: 10.1016/j.jaci.2023.11.024. View

19.

Saenz S, Siracusa M, Perrigoue J, Spencer S, Urban Jr J, Tocker J . IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses. Nature. 2010; 464(7293):1362-6. PMC: 2861732. DOI: 10.1038/nature08901. View

20.

Gogoi M, Clark P, Ferreira A, Rodriguez Rodriguez N, Heycock M, Ko M . ILC2-derived LIF licences progress from tissue to systemic immunity. Nature. 2024; 632(8026):885-892. PMC: 11338826. DOI: 10.1038/s41586-024-07746-w. View