Increased circulating Th17 cells and altered CD4 T cell maturation and differentiation in active tuberculosis with type 2 diabetes: a pilot study

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-10-05T16:33:39Z
Fecha de publicación2025-01-01
ResumenIntroduction Type 2 diabetes (T2D) is a major risk factor for developing tuberculosis (TB). However, understanding the role of defective T cell responses in T2D and TB has been difficult, largely due to inconsistencies across studies. These discrepancies often stem from T cell subset classification primarily relying on cytokine expression profiles, which may not fully capture the complexity of T cell maturation, differentiation, and function in TB patients with T2D.Objective and methods In this pilot study, we sought to identify alterations in phenotypic and ex vivo responses of CD4 T cells to Mycobacterium tuberculosis (Mtb) antigens in people with TB with or without T2D. We evaluated peripheral blood mononuclear cells (PBMC) by high-parameter spectral flow cytometry and assessed T cell differentiation using a cytokine agnostic approach based on validated cell surface markers expression.Results We found major alterations in specific CD4 T cell properties by T2D status, despite no difference in the frequency of bulk CD4 or CD8 T cells. TB-T2D patients (vs TB alone) had fewer circulating na \& iuml;ve CD4 T cells, higher frequency CD4 T cell responses to Mtb antigens, and increased circulating Th1 and three subsets of Th17 cells. Multivariable analysis confirmed that T2D was independently associated with these alterations in maturation state, differentiation phenotype, and the activation of Mtb antigen-responsive CD4 T cells.Conclusion This pilot study reveals CD4 T cell alterations in T2D that likely worsen TB outcomes. A reduced na \& iuml;ve CD4 T cell pool, increased central memory and antigen-activated CD4 T cells, and elevated Th1 and three Th17 cell subsets suggest a pro-inflammatory environment favoring responses that may promote, rather than control TB. These findings highlight immune dysfunctions that could be targeted by host-directed therapies to prevent TB and improve outcomes in T2D patients.es_ES
Doihttps://doi.org/10.3389/fimmu.2025.1637868es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/5464
Idiomaenes_ES
EditorialFRONTIERS MEDIA SAes_ES
RelaciónFrontiers in Immunologyes_ES
URL relacionadohttps://doi.org/10.3389/fimmu.2025.1637868es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteFrontiers in Immunology
Palabra claveTh17 cell subsetses_ES
Palabra clavetuberculosises_ES
Palabra clavetype 2 diabeteses_ES
Palabra clavedysregulatedes_ES
Palabra claveT cell maturationes_ES
TítuloIncreased circulating Th17 cells and altered CD4 T cell maturation and differentiation in active tuberculosis with type 2 diabetes: a pilot studyes_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorOgongo, Paul
AutorMartinez-Lopez, Yoscelina E.
AutorTran, Anthony
AutorLindestam Arlehamn, Cecilia S.
AutorSette, Alessandro
AutorDominguez-Trejo, Ilse A.
AutorGarza, Lizette
AutorCruz-Gonzalez, America M.
AutorLoera-Salazar, Raul
AutorRodriguez-Herrera, Javier E.
AutorAguillon-Duran, Genesis P.
AutorGarcia-Oropesa, Esperanza M.
AutorErnst, Joel D.
AutorRestrepo, Blanca I.
AutorOgongo, Paules_ES
AutorMartinez-Lopez, Yoscelina E.es_ES
AutorTran, Anthonyes_ES
AutorLindestam Arlehamn, Cecilia S.es_ES
AutorSette, Alessandroes_ES
AutorDominguez-Trejo, Ilse A.es_ES
AutorGarza, Lizettees_ES
AutorCruz-Gonzalez, America M.es_ES
AutorLoera-Salazar, Raules_ES
AutorRodriguez-Herrera, Javier E.es_ES
AutorAguillon-Duran, Genesis P.es_ES
AutorGarcia-Oropesa, Esperanza M.es_ES
AutorErnst, Joel D.es_ES
AutorRestrepo, Blanca I.es_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
URL relacionadahttps://doi.org/10.3389/fimmu.2025.1637868
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen16es_ES

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