Elodie Bal

Pediatric inflammatory skin disorders: mechanisms and therapeutic implications

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10.03.2025

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Elodie Bal

Scleroderma: a model for understanding fibrosis

Fibrosis is a physiological tissue repair process. In various pathological conditions, this complex mechanism can be altered, leading to excessive accumulation of extracellular matrix, a major cause of morbidity and mortality in many chronic inflammatory diseases. The progressive and irreversible nature of this dysfibrogenesis represents a major clinical challenge in the absence of curative treatment. Our laboratory is dedicated to studying the molecular and cellular mechanisms involved in the deregulation of fibrogenesis, adopting an innovative, integrative approach. Scleroderma, a group of rare and incurable diseases, is used as a study model to decipher these pathological processes and identify new therapeutic targets and strategies.

Scleroderma is a group of rare, complex and heterogeneous multifactorial diseases characterised by constant abnormal fibrosis of the skin and potentially of internal organs, leading to significant disability, particularly motor disability, with a life-threatening prognosis. A distinction is made between localised cutaneous sclerosis, or morphea, and systemic scleroderma. Both forms are associated with an increased risk of developing cancer. Despite the identification of certain genetic susceptibility factors, the underlying pathophysiological mechanisms remain poorly understood. Scleroderma represents a genuine model for the study of dysfribrogenesis, which is useful for other groups of fibrosing diseases.

Key words :

genetics, epigenetics, mechanisms of cutaneous fibrosis, paediatric-onset scleroderma, new therapeutic targets

In this context, our laboratory has developed 4 main areas of research:

Identification of the genetic alterations involved in severe forms of paediatric scleroderma. Our cohort, which is constantly being enriched thanks to our collaboration with the clinical departments of Hôpital Necker-Enfants Malades, enables us to carry out an in-depth study of these early and aggressive forms.
Deciphering the molecular and cellular mechanisms underlying patients' phenotypes and involved in the progression of the fibrosing process.
Analysing the signalling pathways and cells involved in fibrosis, in particular using single-cell transcriptomic approaches.
The development of a 3-D model of cutaneous fibrosis to evaluate future therapeutic approaches.

Through the study of rare and severe forms of early-onset scleroderma, which are often severe and beyond current therapeutic resources, our aim is to gain a deeper understanding of the key mechanisms of the fibrosing process. This approach aims to open up new therapeutic prospects for these rare incurable diseases, while also benefiting other more common fibrotic diseases that share common mechanisms.

Our study is supported by the ATIP-Avenir programme, the French Dermatology Society and the French Scleroderma Association.