Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy

Xiaoli Hu; Christian S. Buhl; Marie B. Sjogaard; Karoline Schousboe; Hatice I. Mizrak; Huda Kufaishi; Christian S. Hansen; Knud B. Yderstræde; Troels S. Jensen; Jens R. Nyengaard; Pall Karlsson

doi:10.1212/NXI.0000000000200144

Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy

Xiaoli Hu, Christian S. Buhl, Marie B. Sjogaard, Karoline Schousboe, Hatice I. Mizrak, Huda Kufaishi, Christian S. Hansen, Knud B. Yderstræde, Troels S. Jensen, Jens R. Nyengaard, Pall Karlsson

Department of Clinical Medicine - Core Centre for Molecular Morphology, Section for Stereology and Microscopy
Department of Clinical Medicine - SDCA-Steno Diabetes Center Aarhus
Department of Clinical Medicine - The Danish Pain Research Center

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

6 Citations (Scopus)

Abstract

BACKGROUND AND OBJECTIVES: Diabetic polyneuropathy (DPN) is a complication of diabetes characterized by pain or lack of peripheral sensation, but the underlying mechanisms are not yet fully understood. Recent evidence showed increased cutaneous macrophage infiltration in patients with type 2 diabetes and painful DPN, and this study aimed to understand whether the same applies to type 1 diabetes. METHODS: The study included 104 participants: 26 healthy controls and 78 participants with type 1 diabetes (participants without DPN [n = 24], participants with painless DPN [n = 29], and participants with painful DPN [n = 25]). Two immune cells, dermal IBA1+ macrophages and epidermal Langerhans cells (LCs, CD207+), were visualized and quantified using immunohistological labeling and stereological counting methods on skin biopsies from the participants. The IBA1+ macrophage infiltration, LC number density, LC soma cross-sectional area, and LC processes were measured in this study. RESULTS: Significant difference in IBA1+ macrophage expression was seen between the groups (p = 0.003), with lower expression of IBA1 in participants with DPN. No differences in LC morphologies (LC number density, soma cross-sectional area, and process level) were found between the groups (all p > 0.05). In addition, IBA1+ macrophages, but not LCs, correlated with intraepidermal nerve fiber density, Michigan neuropathy symptom inventory, (questionnaire and total score), severity of neuropathy as assessed by the Toronto clinical neuropathy score, and vibration detection threshold in the whole study cohort. DISCUSSION: This study showed expressional differences of cutaneous IBA1+ macrophages but not LC in participants with type 1 diabetes-induced DPN compared with those in controls. The study suggests that a reduction in macrophages may play a role in the development and progression of autoimmune-induced diabetic neuropathy.

Original language	English
Article number	e200144
Journal	Neurology(R) neuroimmunology & neuroinflammation
Volume	10
Issue	5
DOIs	https://doi.org/10.1212/NXI.0000000000200144
Publication status	Published - 1 Aug 2023

Access to Document

10.1212/NXI.0000000000200144Licence: CC BY-NC-ND

Cite this

Hu, X., Buhl, C. S., Sjogaard, M. B., Schousboe, K., Mizrak, H. I., Kufaishi, H., Hansen, C. S., Yderstræde, K. B., Jensen, T. S., Nyengaard, J. R., & Karlsson, P. (2023). Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy. Neurology(R) neuroimmunology & neuroinflammation, 10(5), Article e200144. https://doi.org/10.1212/NXI.0000000000200144

@article{9bde7e28e4a84f7cbd315e2c5702d548,

title = "Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy",

abstract = "BACKGROUND AND OBJECTIVES: Diabetic polyneuropathy (DPN) is a complication of diabetes characterized by pain or lack of peripheral sensation, but the underlying mechanisms are not yet fully understood. Recent evidence showed increased cutaneous macrophage infiltration in patients with type 2 diabetes and painful DPN, and this study aimed to understand whether the same applies to type 1 diabetes. METHODS: The study included 104 participants: 26 healthy controls and 78 participants with type 1 diabetes (participants without DPN [n = 24], participants with painless DPN [n = 29], and participants with painful DPN [n = 25]). Two immune cells, dermal IBA1+ macrophages and epidermal Langerhans cells (LCs, CD207+), were visualized and quantified using immunohistological labeling and stereological counting methods on skin biopsies from the participants. The IBA1+ macrophage infiltration, LC number density, LC soma cross-sectional area, and LC processes were measured in this study. RESULTS: Significant difference in IBA1+ macrophage expression was seen between the groups (p = 0.003), with lower expression of IBA1 in participants with DPN. No differences in LC morphologies (LC number density, soma cross-sectional area, and process level) were found between the groups (all p > 0.05). In addition, IBA1+ macrophages, but not LCs, correlated with intraepidermal nerve fiber density, Michigan neuropathy symptom inventory, (questionnaire and total score), severity of neuropathy as assessed by the Toronto clinical neuropathy score, and vibration detection threshold in the whole study cohort. DISCUSSION: This study showed expressional differences of cutaneous IBA1+ macrophages but not LC in participants with type 1 diabetes-induced DPN compared with those in controls. The study suggests that a reduction in macrophages may play a role in the development and progression of autoimmune-induced diabetic neuropathy.",

author = "Xiaoli Hu and Buhl, {Christian S.} and Sjogaard, {Marie B.} and Karoline Schousboe and Mizrak, {Hatice I.} and Huda Kufaishi and Hansen, {Christian S.} and Yderstr{\ae}de, {Knud B.} and Jensen, {Troels S.} and Nyengaard, {Jens R.} and Pall Karlsson",

year = "2023",

month = aug,

day = "1",

doi = "10.1212/NXI.0000000000200144",

language = "English",

volume = "10",

journal = "Neurology(R) neuroimmunology & neuroinflammation",

issn = "2332-7812",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "5",

}

Hu, X, Buhl, CS, Sjogaard, MB, Schousboe, K, Mizrak, HI, Kufaishi, H, Hansen, CS, Yderstræde, KB, Jensen, TS , Nyengaard, JR & Karlsson, P 2023, 'Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy', Neurology(R) neuroimmunology & neuroinflammation, vol. 10, no. 5, e200144. https://doi.org/10.1212/NXI.0000000000200144

Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy. / Hu, Xiaoli; Buhl, Christian S.; Sjogaard, Marie B. et al.
In: Neurology(R) neuroimmunology & neuroinflammation, Vol. 10, No. 5, e200144, 01.08.2023.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy

AU - Hu, Xiaoli

AU - Buhl, Christian S.

AU - Sjogaard, Marie B.

AU - Schousboe, Karoline

AU - Mizrak, Hatice I.

AU - Kufaishi, Huda

AU - Hansen, Christian S.

AU - Yderstræde, Knud B.

AU - Jensen, Troels S.

AU - Nyengaard, Jens R.

AU - Karlsson, Pall

PY - 2023/8/1

Y1 - 2023/8/1

N2 - BACKGROUND AND OBJECTIVES: Diabetic polyneuropathy (DPN) is a complication of diabetes characterized by pain or lack of peripheral sensation, but the underlying mechanisms are not yet fully understood. Recent evidence showed increased cutaneous macrophage infiltration in patients with type 2 diabetes and painful DPN, and this study aimed to understand whether the same applies to type 1 diabetes. METHODS: The study included 104 participants: 26 healthy controls and 78 participants with type 1 diabetes (participants without DPN [n = 24], participants with painless DPN [n = 29], and participants with painful DPN [n = 25]). Two immune cells, dermal IBA1+ macrophages and epidermal Langerhans cells (LCs, CD207+), were visualized and quantified using immunohistological labeling and stereological counting methods on skin biopsies from the participants. The IBA1+ macrophage infiltration, LC number density, LC soma cross-sectional area, and LC processes were measured in this study. RESULTS: Significant difference in IBA1+ macrophage expression was seen between the groups (p = 0.003), with lower expression of IBA1 in participants with DPN. No differences in LC morphologies (LC number density, soma cross-sectional area, and process level) were found between the groups (all p > 0.05). In addition, IBA1+ macrophages, but not LCs, correlated with intraepidermal nerve fiber density, Michigan neuropathy symptom inventory, (questionnaire and total score), severity of neuropathy as assessed by the Toronto clinical neuropathy score, and vibration detection threshold in the whole study cohort. DISCUSSION: This study showed expressional differences of cutaneous IBA1+ macrophages but not LC in participants with type 1 diabetes-induced DPN compared with those in controls. The study suggests that a reduction in macrophages may play a role in the development and progression of autoimmune-induced diabetic neuropathy.

AB - BACKGROUND AND OBJECTIVES: Diabetic polyneuropathy (DPN) is a complication of diabetes characterized by pain or lack of peripheral sensation, but the underlying mechanisms are not yet fully understood. Recent evidence showed increased cutaneous macrophage infiltration in patients with type 2 diabetes and painful DPN, and this study aimed to understand whether the same applies to type 1 diabetes. METHODS: The study included 104 participants: 26 healthy controls and 78 participants with type 1 diabetes (participants without DPN [n = 24], participants with painless DPN [n = 29], and participants with painful DPN [n = 25]). Two immune cells, dermal IBA1+ macrophages and epidermal Langerhans cells (LCs, CD207+), were visualized and quantified using immunohistological labeling and stereological counting methods on skin biopsies from the participants. The IBA1+ macrophage infiltration, LC number density, LC soma cross-sectional area, and LC processes were measured in this study. RESULTS: Significant difference in IBA1+ macrophage expression was seen between the groups (p = 0.003), with lower expression of IBA1 in participants with DPN. No differences in LC morphologies (LC number density, soma cross-sectional area, and process level) were found between the groups (all p > 0.05). In addition, IBA1+ macrophages, but not LCs, correlated with intraepidermal nerve fiber density, Michigan neuropathy symptom inventory, (questionnaire and total score), severity of neuropathy as assessed by the Toronto clinical neuropathy score, and vibration detection threshold in the whole study cohort. DISCUSSION: This study showed expressional differences of cutaneous IBA1+ macrophages but not LC in participants with type 1 diabetes-induced DPN compared with those in controls. The study suggests that a reduction in macrophages may play a role in the development and progression of autoimmune-induced diabetic neuropathy.

UR - http://www.scopus.com/inward/record.url?scp=85166100304&partnerID=8YFLogxK

U2 - 10.1212/NXI.0000000000200144

DO - 10.1212/NXI.0000000000200144

M3 - Journal article

C2 - 37527931

AN - SCOPUS:85166100304

SN - 2332-7812

VL - 10

JO - Neurology(R) neuroimmunology & neuroinflammation

JF - Neurology(R) neuroimmunology & neuroinflammation

IS - 5

M1 - e200144

ER -

Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy

Abstract

Access to Document

Other files and links

Fingerprint

Cite this