Intracellular cytokine levels and HLA-DR expression by innate lymphoid cells in health and allergy
Download article
E.A. Pashkina, O.S. Boeva, V.S. Abbasova, A.A. Aktanova, D.V. Demina, L.V. Grishina, V.A. Kozlov
Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
Abstract
The growing prevalence of allergic diseases, such as bronchial asthma and atopic dermatitis, represents a pressing issue in modern medicine. In the development of allergen sensitization in these diseases, polarization of the type 2 immune response is observed in most cases; type 2 T helper cells and the recently discovered type 2 innate lymphoid cells regulate this response. The aim of the study was to evaluate the intracellular cytokine content of ILCs and their expression of HLA-DR in blood mononuclear cell cultures, with and without stimulation, in patients with allergic diseases and in healthy controls. Mononuclear cells were cultured in complete RPMI-1640 medium in the presence of LPS or PMA/ionomycin. Cell cultures without added activators served as controls. Mononuclear cell phenotyping was performed by flow cytometry. Patients with allergic diseases were found to have an increased proportion of IFNγ+ ILC1 in the absence of stimulation, as well as an increased proportion of IL-5+ ILC2 upon stimulation with PMA/ionomycin, compared with the control group. Furthermore, patients with allergic pathology showed a higher density of HLA-DR expression on ILC3 upon stimulation with LPS. Such changes may influence the polarization of the immune response to an antigen and alter the interaction between ILCs and T cells in patients with allergic pathology compared with healthy controls.
Keywords: cytokines, innate lymphoid cells, antigen presentation, allergy, asthma
There is no conflict of interest.
Contact information of the author responsible for correspondence
Ekaterina A. Pashkina
pashkina.e.a@yandex.ru
Received: 30.06.2026
For citation
Pashkina E.A., Boeva O.S., Abbasova V.S., Aktanova A.A., Demina D.V., Grishina L.V., Kozlov V.A. Intracellular cytokine levels and HLA-DR expression by innate lymphoid cells in health and allergy. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2026, Vol. 23, no. 3, pp. 445-457. DOI: 10.22138/2500-0918-2026-23-3-445-457 (In Russ)
Funding
This work was supported by the Russian Science Foundation under RSF Project No. 24-15-00409.
REFERENCES
- Shin Y.H., Hwang J., Kwon R., Lee S.W., Kim M.S.; GBD 2019 Allergic Disorders Collaborators; Shin J.I., Yon D.K. Global, regional, and national burden of allergic disorders and their risk factors in 204 countries and territories, from 1990 to 2019: A systematic analysis for the Global Burden of Disease Study 2019. Allergy. 2023;78(8): 2232-2254. doi: 10.1111/all.15807
- Alska E., Doligalska A., Napiórkowska-Baran K., Dolina M., Osińska K., Pilichowicz A., et al. Global Burden of Allergies: Mechanisms of Development, Challenges in Diagnosis, and Treatment. Life (Basel). 2025;15(6): 878. doi: 10.3390/life15060878
- Ogulur I., Mitamura Y., Yazici D., Pat Y., Ardicli S., Li M., et al. Type 2 immunity in allergic diseases. Cellular & Molecular Immunology. 2025;22(3): 211-242. doi: 10.1038/s41423-025-01261-2
- Huang Y., Paul W.E. Inflammatory group 2 innate lymphoid cells. International Immunology. 2016;28(1): 23-28. doi: 10.1093/intimm/dxv044
- Morita H., Moro K., Koyasu S. Innate lymphoid cells in allergic and nonallergic inflammation. Journal of Allergy and Clinical Immunology. 2016;138(5): 1253-1264. doi: 10.1016/j.jaci.2016.09.011
- Kim H.Y., Umetsu D.T., Dekruyff R.H. Innate lymphoid cells in asthma: Will they take your breath away? European Journal of Immunology. 2016;46(4): 795-806. doi: 10.1002/eji.201546194
- Smith S.G., Chen R., Kjarsgaard M., Huang C., Oliveria J.P., O'Byrne P.M., et al. Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. Journal of Allergy and Clinical Immunology. 2016;137(1): 75-86.e8. doi: 10.1016/j.jaci.2015.05.037
- Bergot A.S., Monnet N., Le Tran S., Mittal D., Al-Kouba J., Steptoe R.J., et al. HPV16 E7 expression in skin induces TSLP secretion, type 2 ILC infiltration and atopic dermatitis-like lesions. Immunology and Cell Biology. 2015;93(6): 540-547. doi: 10.1038/icb.2014.121
- Fan D., Wang X., Wang M., Wang Y., Zhang L., Li Y., et al. Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis. Allergy, Asthma & Immunology Research. 2016;8(3): 216-222. doi: 10.4168/aair.2016.8.3.216
- Bartemes K.R., Kita H. Roles of innate lymphoid cells (ILCs) in allergic diseases: The 10-year anniversary for ILC2s. Journal of Allergy and Clinical Immunology. 2021;147(5): 1531-1547. doi: 10.1016/j.jaci.2021.03.015
- Robinette M.L., Colonna M. Innate lymphoid cells and the MHC. HLA. 2016;87(1): 5-11. doi: 10.1111/tan.12723
- Oliphant C.J., Hwang Y.Y., Walker J.A., Salimi M., Wong S.H., Brewer J.M., et al. MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity. 2014;41(2): 283-295. doi: 10.1016/j.immuni.2014.06.016
- Calabrò A., Yamazaki S., Ferlazzo G., Campana S. The Antigen Presenting Capabilities of Group 3 Innate Lymphoid Cells: Insights Into Immunogenic or Tolerogenic Outcomes for T Cells. European Journal of Immunology. 2025;55(12): e70103. doi: 10.1002/eji.70103
- von Burg N., Chappaz S., Baerenwaldt A., Horvath E., Bose Dasgupta S., Ashok D., et al. Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(35): 12835-12840. doi: 10.1073/pnas.1406908111
- Hepworth M.R., Fung T.C., Masur S.H., Kelsen J.R., McConnell F.M., Dubrot J., et al. Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4(+) T cells. Science. 2015;348(6238): 1031-1035. doi: 10.1126/science.aaa4812
- Hepworth M.R., Monticelli L.A., Fung T.C., Ziegler C.G., Grunberg S., Sinha R., et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature. 2013;498(7452): 113-117. doi: 10.1038/nature12240
- Melo-Gonzalez F., Kammoun H., Almeida C.F., Platten M., Kurz T., Rühle M., et al. Antigen-presenting ILC3 regulate T cell-dependent IgA responses to colonic mucosal bacteria. Journal of Experimental Medicine. 2019;216(4): 728-742. doi: 10.1084/jem.20180871
- Lehmann F.M., von Burg N., Ivanek R., Teufel C., Horvath E., Peter A., et al. Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation. Nature Communications. 2020;11(1): 1794. doi: 10.1038/s41467-020-15612-2
- Drake L.Y., Iijima K., Kita H. Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice. Allergy. 2014;69(10): 1300-1307. doi: 10.1111/all.12446
- Mirchandani A.S., Besnard A.-G., Yip E., Scott C., Bain C.C., Cerovic V., et al. Type 2 innate lymphoid cells drive CD4+ Th2 cell responses. Journal of Immunology. 2014;192(5): 2442-2448. doi: 10.4049/jimmunol.1300974
- Liu B., Lee J.-B., Chen C.-Y., Hershey G.K.K., Wang Y.-H. Collaborative interactions between type 2 innate lymphoid cells and antigen-specific CD4+ Th2 cells exacerbate murine allergic airway diseases with prominent eosinophilia. Journal of Immunology. 2015;194(8): 3583-3593. doi: 10.4049/jimmunol.1400951
- Halim T.Y.F., Rana B.M.J., Walker J.A., Kerscher B., Knolle M.D., Jolin H.E., et al. Tissue-restricted adaptive type 2 immunity is orchestrated by expression of the costimulatory molecule OX40L on group 2 innate lymphoid cells. Immunity. 2018;48(6): 1195-1207.e6. doi: 10.1016/j.immuni.2018.05.003
- Hardman C.S., Chen Y.-L., Salimi M., Jarrett R., Johnson D., Järvinen V.J., et al. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells. Science Immunology. 2017;2(18): eaan5918. doi: 10.1126/sciimmunol.aan5918
- Hazenberg M.D., Spits H. Human innate lymphoid cells. Blood. 2014;124(5): 700-709. doi: 10.1182/blood-2013-11-427781
- Zheng H., Zhang Y., Pan J., Liu N., Qin Y., Qiu L., et al. The Role of Type 2 Innate Lymphoid Cells in Allergic Diseases. Frontiers in Immunology. 2021;12: 586078. doi: 10.3389/fimmu.2021.586078
- Biedermann T., Skabytska Y., Kaesler S., Volz T. Regulation of T Cell Immunity in Atopic Dermatitis by Microbes: The Yin and Yang of Cutaneous Inflammation. Frontiers in Immunology. 2015;6: 353. doi: 10.3389/fimmu.2015.00353
- Wasserer S., Jargosch M., Mayer K.E., Eigemann J., Raunegger T., Aydin G., et al. Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis. International Journal of Molecular Sciences. 2024;25(11): 6158. doi: 10.3390/ijms25116158
Authors
Ekaterina A. Pashkina
Cand. Sci. (Biol.), Head of Laboratory
pashkina.e.a@yandex.ru
Olga S. Boeva
Postgraduate Student, Research Lab Assistant
starchenkova97@gmail.com
Veronika S. Abbasova
Resident, Research Lab Assistant
abbasovaveronik@gmail.com
Alina A. Aktanova
Researcher
aktanova_al@mail.ru
Daria V. Demina
Cand. Sci. (Med.), Head of the Allergology Department, Immunopathology Clinic
immunology@mail.ru
Lyubov V. Grishina
Cand. Sci. (Biol.), Researcher
1_grishina@bk.ru
Vladimir A. Kozlov
Academician of the Russian Academy of Sciences, Professor, Dr. Sci. (Med.), Scientific Director of the Institute
vakoz40@yandex.ru
Research Institute of Fundamental and Clinical Immunology (RIFCI)
Novosibirsk, Russian Federation