Differential expression of TLR2 and TLR4 in α4β7-positive leukocytes of patients with axial spondyloarthritis

Romero-López, José Pablo; Gómez-Martínez, David; Domínguez-López, María Lilia; Jiménez-Zamudio, L; Casasola-Vargas, Julio; Burgos‐Vargas, Rubén; Garcı́a-Latorre, Ethel

doi:10.1093/rheumatology/kez364

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…Further proof supporting the importance of the gut–joint axis in the SpA pathogenetic process is the evidence that in the PB of patients compared with controls, even when the total number of γδ T cells was reduced, there was an increased frequency of γδ T cells expressing on their surface the intestinal homing receptor α4β7. In this regard, these cells, once activated in the gut due to a microbiome impairment, may migrate to peripheral tissues such as joints, where high levels of MAdCAM1 could regulate this process [ 99 ]. The role of the innate immune system in axial-SpA pathogenesis is depicted in Figure 2 .…”

Section: Role Of Innate Immunitymentioning

confidence: 99%

Uncovering the Underworld of Axial Spondyloarthritis

Vescovo

Venerito

Iannone

et al. 2023

IJMS

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Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.

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Section: Role Of Innate Immunitymentioning

confidence: 99%

Uncovering the Underworld of Axial Spondyloarthritis

Vescovo

Venerito

Iannone

et al. 2023

IJMS

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“…Aproximadamente la mitad de los pacientes con SpA tienen inflamación intestinal subclínica evidenciada por estudios histológicos 61 y por el aumento de calprotectina fecal y sérica 62,63 . Se ha propuesto que el intestino es el sitio desde el cual se originan las células y citocinas inflamatorias responsables de la artritis y de la osteoproliferación de estos pacientes.…”

Section: Espondiloartritisunclassified

“…Se ha reportado evidencia de que los pacientes con EA presentan una expansión de células ILC3 productoras de IL-17 e IL-22 en el intestino, líquido sinovial y médula ósea 84 . Por otro lado, un estudio reciente de nuestro grupo de investigación demostró que en pacientes con axSpA las células Tγδ presentes en sangre, tienen una expresión aumentada de la integrina α4β7 y de los receptores TLR2 y TLR4 (receptores asociados al reconocimiento de patrones) en comparación con donadores sanos 63 . Esto respalda la hipótesis de que una alta expresión de la integrina α4β7 en linfocitos Tγδ activados en el intestino permite su migración hacia la circulación y en su trayecto es posible que se dirijan hacia la articulación para salir del torrente sanguíneo, residir en el tejido articular y desencadenar procesos inflamatorios.…”

Section: Integración Del Eje Intestino-pielarticulaciónunclassified

Papel del eje intestino-piel-articulaci�n en enfermedades inmunomediadas. Papel de nuevas terapias con JAKinibs selectivos e inhibidores IL23p19

Bernal-Alferes¹,

Basilio-Aguilar²,

Domínguez-López³

et al. 2021

IMIDS

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Illuminating the impact of γδ T cells in man and mice in spondylarthritides

Meyer

2024

Eur J Immunol

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Spondylarthritides (SpA) are a group of autoinflammatory diseases affecting the spine, peripheral joints, and entheses, including axial spondyloarthritis (axSpA) and psoriatic arthritis. AxSpA has a multifactorial etiology that involves genetic predispositions, such as HLA‐B27 and IL‐23R. Although HLA‐B27 is strongly associated with axSpA, its role remains unclear. GWAS studies have demonstrated that genetic polymorphisms related to the IL‐23 pathway occur throughout the spectrum of SpA, including but not limited to axSpA and PsA. IL‐23 promotes the production of IL‐17, which drives inflammation and tissue damage. This pathway contributes not only to peripheral enthesitis but also to spinal inflammation. γδ T cells in axSpA express IL‐23R and RORγt, crucial for their activation, although specific pathogenic cells and factors remain elusive. Despite drug efficacy in PsA, IL‐23R inhibition is ineffective in axSpA. Murine models provide valuable insights into the intricate cellular and molecular interactions that contribute to the development and progression of SpA. Those models are useful tools to elucidate the dynamics of γδ T cell involvement, offering insights into disease mechanisms and potential therapeutic targets. This review aims to illuminate the complex interplay between IL‐23 and γδ T cells in SpA pathogenesis, emphasizing their roles in chronic inflammation, tissue damage, and disease heterogeneity.

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Differential expression of TLR2 and TLR4 in α4β7-positive leukocytes of patients with axial spondyloarthritis

Cited by 5 publications

References 40 publications

Uncovering the Underworld of Axial Spondyloarthritis

Uncovering the Underworld of Axial Spondyloarthritis

Papel del eje intestino-piel-articulaci�n en enfermedades inmunomediadas. Papel de nuevas terapias con JAKinibs selectivos e inhibidores IL23p19

Illuminating the impact of γδ T cells in man and mice in spondylarthritides

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