Role of CXCR3/CXCL10 Axis in Immune Cell Recruitment into the Small Intestine in Celiac Disease

Bondar, Constanza; Araya, Romina Elizabeth; Guzmán, Luciana; Rúa, Eduardo Cueto; Chopita, N; Chirdo, Fernando Gabriel

doi:10.1371/journal.pone.0089068

Cited by 68 publications

(71 citation statements)

References 35 publications

(54 reference statements)

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“…However, we observed the opposite, that is, a higher concentration of CXCL10 was associated with FA. Interestingly, CXCL10/CXCR3 signaling axis is overactivated in the small intestine of active celiac patients, participating in lymphocytic recruitment, suggesting an inflammatory role of this chemokine in the intestine . It is also noteworthy that CXCL10 has an antibacterial role: A negative effect of high concentrations of CXCL10 on microbiota shaping/implantation therefore warrants further attention.…”

Section: Discussionmentioning

confidence: 99%

Immune components of early breastmilk: Association with maternal factors and with reported food allergy in childhood

Berdi

Lauzon-Guillain

Forhan

et al. 2019

Pediatric Allergy Immunology

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Background Breastmilk (BM) may participate in driving gut barrier function and immunity in the neonate. We analyzed immune and growth factor concentrations in early BM and their association with maternal/environmental characteristics and with food allergy (FA) in childhood. Methods One BM sample was collected in maternity from some mothers in the EDEN birth cohort (n = 2002 mother‐child dyads). A random selection was performed among available samples (subcohort, n = 272), for which all deliveries were full‐term, various maternal/environmental characteristics were recorded, and parents answered yearly the question “Has a medical doctor diagnosed a FA in your child?” (26 parent‐reported FA cases). Only samples collected between day 2 and day 6 post‐partum were considered for descriptive analysis (n = 263). Samples for all other FA cases available were added to the subcohort (46 additional cases; “casecohort” design). Fifty cytokines, antibodies, and growth factor concentrations were determined using multiplexed kits and analyzed using robust statistical procedures. Results BM components exhibited wide concentration ranges and global day‐to‐day variation. Different clusters of correlated factors appeared, with components from the main cluster related to maternal diet during pregnancy. Primiparity was positively associated with eleven other components, whereas other factors (eg, maternal atopy and smoking) were related to fewer components. Finally, the casecohort design highlighted a positive association between CXCL10, TNFβ, and IL‐2 concentrations and reported FA in childhood. Conclusion Beyond the unique description of early BM composition, we show that immune information transmitted to the neonate is related to various maternal factors and identified components associated with FA diagnosis in childhood.

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Section: Discussionmentioning

confidence: 99%

Immune components of early breastmilk: Association with maternal factors and with reported food allergy in childhood

Berdi

Lauzon-Guillain

Forhan

et al. 2019

Pediatric Allergy Immunology

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“…70 CXCR3/CXCL10 signaling has been suggested to be one of the most relevant pathways in the attraction of immune cells such as monocytes/macrophages, T cells, natural killer (NK) cells, and dendritic cells to inflamed tissues. 71 It also has been demonstrated that CXCR3/CXCL10 signaling is crucial in microglia recruitment. 72 Although not exhaustive, these results provide one clue about a potentially important molecular mechanism to enhance brain engraftment following BMT.…”

Section: Discussionmentioning

confidence: 99%

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice

Yang

Aloi

Cudaback

et al. 2014

Laboratory Investigation

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Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy. Bone marrow-derived cells are able to engraft in the brain and adopt a microglial phenotype under myeloablative irradiation conditioning. This ability makes bone marrow (BM)-derived cells a potential cellular vehicle for transferring therapeutic molecules to the central nervous system. Here, we utilized BM cells from Grn+/+ (wild type or wt) mice labeled with green fluorescence protein for delivery of progranulin to progranulin deficient (Grn−/−) mice. Our results showed that wt bone marrow transplantation (BMT) partially reconstituted progranulin in the periphery and in cerebral cortex of Grn−/− mice. We demonstrated a pro-inflammatory effect in vivo and in ex vivo preparations of cerebral cortex of Grn−/− mice that was partially to fully reversed five months after BMT. Our findings suggest that BMT can be administered as a stem cell-based approach to prevent or to treat neurodegenerative diseases.

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“…CXCL10 (IP‐10) is an IFN‐γ‐inducible protein produced by T cells, NK and NKT cells, monocytes and DCs but also by fibroblasts and endothelial cells (Bondar et al , ). It is particularly important in chronic inflammation, including atherosclerosis and hypertension (Ide et al , ).…”

Section: Chemokines In Pvat Inflammationmentioning

confidence: 99%

Perivascular adipose tissue inflammation in vascular disease

Nosalski

Guzik

2017

British J Pharmacology

287

237

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Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies, perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vasoprotective adipocyte-derived relaxing factors and increased production of paracrine factors such as resistin, leptin, cytokines (IL-6 and TNF-α) and chemokines [RANTES (CCL5) and MCP-1 (CCL2)]. These adipocyte-derived factors initiate and orchestrate inflammatory cell infiltration including primarily T cells, macrophages, dendritic cells, B cells and NK cells. Protective factors such as adiponectin can reduce NADPH oxidase superoxide production and increase NO bioavailability in the vessel wall, while inflammation (e.g. IFN-γ or IL-17) induces vascular oxidases and eNOS dysfunction in the endothelium, vascular smooth muscle cells and adventitial fibroblasts. All of these events link the dysfunctional perivascular fat to vascular dysfunction. These mechanisms are important in the context of a number of cardiovascular disorders including atherosclerosis, hypertension, diabetes and obesity. Inflammatory changes in PVAT's molecular and cellular responses are uniquely different from classical visceral or subcutaneous adipose tissue or from adventitia, emphasizing the unique structural and functional features of this adipose tissue compartment. Therefore, it is essential to develop techniques for monitoring the characteristics of PVAT and assessing its inflammation. This will lead to a better understanding of the early stages of vascular pathologies and the development of new therapeutic strategies focusing on perivascular adipose tissue.

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Role of CXCR3/CXCL10 Axis in Immune Cell Recruitment into the Small Intestine in Celiac Disease

Cited by 68 publications

References 35 publications

Immune components of early breastmilk: Association with maternal factors and with reported food allergy in childhood

Immune components of early breastmilk: Association with maternal factors and with reported food allergy in childhood

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice

Perivascular adipose tissue inflammation in vascular disease

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