The Ultrastructure of Hepatic Stellate Cell-Macrophage Intercellular Crosstalk as a New Morphological Insight into Phenomenon of Fibrogenesis in Pediatric Autoimmune Hepatitis

Joanna Maria Łotowska; Maria Elżbieta Sobaniec-Łotowska; Anna Bobrus-Chociej; Piotr Sobaniec

doi:10.3390/jcm12031024

The Ultrastructure of Hepatic Stellate Cell-Macrophage Intercellular Crosstalk as a New Morphological Insight into Phenomenon of Fibrogenesis in Pediatric Autoimmune Hepatitis

J Clin Med. 2023 Jan 28;12(3):1024. doi: 10.3390/jcm12031024.

Authors

Joanna Maria Łotowska¹, Maria Elżbieta Sobaniec-Łotowska¹, Anna Bobrus-Chociej², Piotr Sobaniec³

Affiliations

¹ Department of Medical Pathomorphology, Faculty of Medicine with the Division of Dentistry and Division of Medical Education in English, Medical University of Bialystok, 15-269 Bialystok, Poland.
² Department of Pediatrics, Gastroenterology, Hepatology, Nutrition and Allergology, Faculty of Medicine with the Division of Dentistry and Division of Medical Education in English, Medical University of Bialystok, 15-274 Bialystok, Poland.
³ Department of Pediatric Neurology, Faculty of Medicine with the Division of Dentistry and Division of Medical Education in English, Medical University of Bialystok, 15-274 Bialystok, Poland.

Abstract

The aim of the study was the pioneering retrospective ultrastructural evaluation of respective forms of hepatic stellate cells (HSCs) and analysis of their crosstalk with other adjacent nonparenchymal cells (NPCs), especially Kupffer cells/macrophages (KCs/MPs), in pediatric autoimmune hepatitis (AIH).

Methods: Ultrastructural assessment of the HSC population and NPCs was performed in transmission electron microscopy (TEM) using pretreatment liver biopsies from 25 children (8 boys and 17 girls) aged 4-17 with clinic-pathologically diagnosed untreated AIH.

Results: Submicroscopic evaluation allowed easy identification of numerous HSCs in the form of transitory cells, i.e., T-HSCs, accompanied by signs of fibrosis. T-HSCs included cells with features of activation initiation (iHSCs) and activation perpetuation (pHSCs), indicating high HSC activation plasticity. The pHSCs were markedly elongated and mainly showed a distinct loss of lipid cytoplasmic material, expanded and dilated channels of granular endoplasmic reticulum, and linear bundles of microfilaments beneath the cell membrane. They were surrounded by usually mature collagen fibers. Frequently activated KCs/MPs adhered directly to T-HSCs. Between them, tight intercellular junctions were formed by means of point desmosomes.

Conclusions: Our qualitative TEM observations indicate a key role of T-HSCs in liver fibrogenesis in pediatric AIH, with the essential involvement of activated KCs/MPs that directly adhere to them. Tight intercellular junctions, being the ultrastructural exponent of the specific cellular mechanisms of the crosstalk between NPCs, can play a vital role in hepatic collagen fibroplasia. A better understanding of HSC population morphology at the ultrastructural level in AIH seems important not only to improve the disease morphological diagnostics but to also provide new insights into therapeutic interventions for the phenomenon of liver fibrogenesis.

Keywords: activated Kupffer cells/macrophages (KCs/MPs); cellular crosstalk; hepatic stellate cell (HSC) population; iHSCs; liver fibrogenesis; nonparenchymal hepatic cells (NPCs); pHSCs; pediatric autoimmune hepatitis (AIH); transitional hepatic stellate cells (T-HSCs); ultrastructural studies.

Grants and funding

This research was supported by a research grant (SUB/1/DN/20/003/1194) from the Medical University of Bialystok, Poland.