Clinical & translational immunology · 2026
Alterations of circulating innate lymphoid cells in recent-onset type 1 diabetes.
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Roig Ariadna, Perna-Barrull David, Aguilera Eva, Pérez Sebastián, Vives-Pi Marta, Planas Raquel
Аннотация
OBJECTIVES: Type 1 diabetes (T1D) is driven by autoreactive T lymphocytes with contributions from innate immune compartments, yet early innate immune alterations associated with autoimmune amplification remain incompletely defined. We aimed at investigating whether circulating innate lymphoid cells (ILCs) contribute to these processes.
METHODS: Circulating ILCs from patients with recent-onset T1D (n = 12) and age-matched healthy donors were analysed by spectral flow cytometry and targeted gene-expression profiling of purified ILC progenitors (ILCP). Metabolic and inflammatory modulation of ILC activation was assessed in vitro. Antigen presentation to autologous memory CD4 T cells was functionally evaluated. Findings were examined across disease progression in NOD mice.
RESULTS: Total ILC frequencies were comparable between groups; however, ILC1 and ILCP from T1D patients displayed increased activation markers (CD69, HLA-DR). ILCP exhibited reduced expression of migratory (CCR7, CCR6) and regulatory-associated genes (ICOS, CD58). Glycolytic inhibition selectively attenuated ILCP activation, supporting a metabolic contribution. IL-1β, and to a lesser extent IFNγ, enhanced antigen presentation-associated phenotypes in human circulating ILCs. Upon inflammatory pre-activation, insulin peptide-loaded circulating ILCs upregulated MHC class II-associated markers and induced antigen-specific activation of autologous CD4⁺ memory T cells. NOD mice recapitulated ILC activation and MHC class II expression patterns during diabetes progression.
CONCLUSION: Circulating ILCs in recent-onset T1D display a pre-activated, metabolically regulated phenotype with functional antigen-presenting capacity, supporting a potential role in autoimmune amplification. The findings of this exploratory study provide translational insight into innate immune dysregulation associated with recent-onset T1D.
METHODS: Circulating ILCs from patients with recent-onset T1D (n = 12) and age-matched healthy donors were analysed by spectral flow cytometry and targeted gene-expression profiling of purified ILC progenitors (ILCP). Metabolic and inflammatory modulation of ILC activation was assessed in vitro. Antigen presentation to autologous memory CD4 T cells was functionally evaluated. Findings were examined across disease progression in NOD mice.
RESULTS: Total ILC frequencies were comparable between groups; however, ILC1 and ILCP from T1D patients displayed increased activation markers (CD69, HLA-DR). ILCP exhibited reduced expression of migratory (CCR7, CCR6) and regulatory-associated genes (ICOS, CD58). Glycolytic inhibition selectively attenuated ILCP activation, supporting a metabolic contribution. IL-1β, and to a lesser extent IFNγ, enhanced antigen presentation-associated phenotypes in human circulating ILCs. Upon inflammatory pre-activation, insulin peptide-loaded circulating ILCs upregulated MHC class II-associated markers and induced antigen-specific activation of autologous CD4⁺ memory T cells. NOD mice recapitulated ILC activation and MHC class II expression patterns during diabetes progression.
CONCLUSION: Circulating ILCs in recent-onset T1D display a pre-activated, metabolically regulated phenotype with functional antigen-presenting capacity, supporting a potential role in autoimmune amplification. The findings of this exploratory study provide translational insight into innate immune dysregulation associated with recent-onset T1D.