Investigating Immune Profile by CyTOF in Individuals with Long-standing Type 1 Diabetes

Overview

Journal Sci Rep

Specialty Science

Date 2023 May 20

PMID 37210405

Authors

Helen Larsson

Sofie Albinsson Hogberg

Marcus Lind

Hardis Rabe

Christine Lingblom

Affiliations

Soon will be listed here.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of pancreatic beta cells. Eosinophils are found in pancreatic tissue from individuals with T1D. Eosinophilic suppression of T cells is dependent of the protein galectin-10. Little is known when it comes to the role of eosinophil granulocytes in type 1 diabetes. Here we show that individuals with long-standing T1D had lower levels of galectin-10 eosinophils and a subgroup of galectin-10 eosinophils were entirely absent in all T1D patients. In addition, 7% immature eosinophils were present in the circulation of T1D patients whereas 0.8% in healthy individuals. Furthermore, higher levels of CD4+CD8+ T cells and Th17 cells were observed in patients with T1D. Blood samples from 12 adult individuals with long-standing T1D and 12 healthy individuals were compared using cytometry by time-of-flight. Lower levels of galectin-10 eosinophils, which are potent T cell suppressors, in individuals with T1D could indicate that activated T cells are enabled to unrestrictedly kill the insulin producing beta cells. This is the first study showing absence of galectin-10 eosinophilic subgroup in individuals with T1D compared with healthy controls. This study is a first important step toward unraveling the role of the eosinophils in patients with T1D.

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References

Ling Q, Shen L, Zhang W, Qu D, Wang H, Wang B . Increased plasmablasts enhance T cell-mediated beta cell destruction and promote the development of type 1 diabetes. Mol Med. 2022; 28(1):18. PMC: 8818172. DOI: 10.1186/s10020-022-00447-y. View

Albinsson S, Lingblom C, Lundqvist C, Telemo E, Ekwall O, Wenneras C . Eosinophils interact with thymocytes and proliferate in the human thymus. Eur J Immunol. 2021; 51(6):1539-1541. DOI: 10.1002/eji.202049080. View

Pellegrini S, Sordi V, Bolla A, Saita D, Ferrarese R, Canducci F . Duodenal Mucosa of Patients With Type 1 Diabetes Shows Distinctive Inflammatory Profile and Microbiota. J Clin Endocrinol Metab. 2017; 102(5):1468-1477. DOI: 10.1210/jc.2016-3222. View

Hessner M, Wang X, Meyer L, Geoffrey R, Jia S, Fuller J . Involvement of eotaxin, eosinophils, and pancreatic predisposition in development of type 1 diabetes mellitus in the BioBreeding rat. J Immunol. 2004; 173(11):6993-7002. DOI: 10.4049/jimmunol.173.11.6993. View

Oram R, Jones A, Besser R, Knight B, Shields B, Brown R . The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells. Diabetologia. 2013; 57(1):187-91. PMC: 3855529. DOI: 10.1007/s00125-013-3067-x. View

Todd J . Etiology of type 1 diabetes. Immunity. 2010; 32(4):457-67. DOI: 10.1016/j.immuni.2010.04.001. View

Okubo Y, Torrey H, Butterworth J, Zheng H, Faustman D . Treg activation defect in type 1 diabetes: correction with TNFR2 agonism. Clin Transl Immunology. 2016; 5(1):e56. PMC: 4735064. DOI: 10.1038/cti.2015.43. View

Kelly E, Koziol-White C, Clay K, Liu L, Bates M, Bertics P . Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma. J Immunol. 2009; 182(3):1404-10. PMC: 2851244. DOI: 10.4049/jimmunol.182.3.1404. View

Ledbetter L, Cherla R, Chambers C, Zhang Y, Zhang G . Eosinophils Affect Antibody Isotype Switching and May Partially Contribute to Early Vaccine-Induced Immunity against Coxiella burnetii. Infect Immun. 2019; 87(11). PMC: 6803328. DOI: 10.1128/IAI.00376-19. View

10.

Sokolowska M, Chobot A, Jarosz-Chobot P . The honeymoon phase - what we know today about the factors that can modulate the remission period in type 1 diabetes. Pediatr Endocrinol Diabetes Metab. 2017; 22(2):66-70. DOI: 10.18544/PEDM-22.02.0053. View

11.

Chu V, Frohlich A, Steinhauser G, Scheel T, Roch T, Fillatreau S . Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol. 2011; 12(2):151-9. DOI: 10.1038/ni.1981. View

12.

Sanford M, McKeage K . Secukinumab: first global approval. Drugs. 2015; 75(3):329-38. DOI: 10.1007/s40265-015-0359-0. View

13.

de Boer P, Pirozzi N, Wolters A, Kuipers J, Kusmartseva I, Atkinson M . Large-scale electron microscopy database for human type 1 diabetes. Nat Commun. 2020; 11(1):2475. PMC: 7235089. DOI: 10.1038/s41467-020-16287-5. View

14.

Mendes-da-Cruz D, Lemos J, Passos G, Savino W . Abnormal T-Cell Development in the Thymus of Non-obese Diabetic Mice: Possible Relationship With the Pathogenesis of Type 1 Autoimmune Diabetes. Front Endocrinol (Lausanne). 2018; 9:381. PMC: 6052664. DOI: 10.3389/fendo.2018.00381. View

15.

Albinsson S, Lingblom C, Lundqvist C, Hennings V, Telemo E, Ekwall O . Distinct populations of eosinophils in the human thymus with capacity to modulate thymocyte maturation. Immunology. 2022; 169(1):57-68. DOI: 10.1111/imm.13610. View

16.

Tulic M, Sly P, Andrews D, Crook M, Davoine F, Odemuyiwa S . Thymic indoleamine 2,3-dioxygenase-positive eosinophils in young children: potential role in maturation of the naive immune system. Am J Pathol. 2009; 175(5):2043-52. PMC: 2774068. DOI: 10.2353/ajpath.2009.090015. View

17.

Cappellari R, DAnna M, Menegazzo L, Bonora B, Albiero M, Avogaro A . Diabetes mellitus impairs circulating proangiogenic granulocytes. Diabetologia. 2020; 63(9):1872-1884. DOI: 10.1007/s00125-020-05142-3. View

18.

Lingblom C, Wallander J, Ingelsten M, Bergquist H, Bove M, Saalman R . Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3. Clin Exp Immunol. 2016; 187(3):455-465. PMC: 5290232. DOI: 10.1111/cei.12898. View

19.

Chatzigeorgiou A, Harokopos V, Mylona-Karagianni C, Tsouvalas E, Aidinis V, Kamper E . The pattern of inflammatory/anti-inflammatory cytokines and chemokines in type 1 diabetic patients over time. Ann Med. 2010; 42(6):426-38. DOI: 10.3109/07853890.2010.495951. View

20.

Forman R, Bramhall M, Logunova L, Svensson-Frej M, Cruickshank S, Else K . Eosinophils may play regionally disparate roles in influencing IgA(+) plasma cell numbers during large and small intestinal inflammation. BMC Immunol. 2016; 17(1):12. PMC: 4886441. DOI: 10.1186/s12865-016-0153-0. View