IL-23 induces CLEC5A+ IL-17A+ neutrophils and elicit skin inflammation associated with psoriatic arthritis.
J Autoimmun
; 143: 103167, 2024 02.
Article
en En
| MEDLINE
| ID: mdl-38301504
ABSTRACT
IL-23-activation of IL-17 producing T cells is involved in many rheumatic diseases. Herein, we investigate the role of IL-23 in the activation of myeloid cell subsets that contribute to skin inflammation in mice and man. IL-23 gene transfer in WT, IL-23RGFP reporter mice and subsequent analysis with spectral cytometry show that IL-23 regulates early innate immune events by inducing the expansion of a myeloid MDL1+CD11b+Ly6G+ population that dictates epidermal hyperplasia, acanthosis, and parakeratosis; hallmark pathologic features of psoriasis. Genetic ablation of MDL-1, a major PU.1 transcriptional target during myeloid differentiation exclusively expressed in myeloid cells, completely prevents IL-23-pathology. Moreover, we show that IL-23-induced myeloid subsets are also capable of producing IL-17A and IL-23R+MDL1+ cells are present in the involved skin of psoriasis patients and gene expression correlations between IL-23 and MDL-1 have been validated in multiple patient cohorts. Collectively, our data demonstrate a novel role of IL-23 in MDL-1-myelopoiesis that is responsible for skin inflammation and related pathologies. Our data open a new avenue of investigations regarding the role of IL-23 in the activation of myeloid immunoreceptors and their role in autoimmunity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Psoriasis
/
Artritis Psoriásica
/
Dermatitis
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Autoimmun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos