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Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum.

Montalvillo E, Bernardo D, Martínez-Abad B, Allegretti Y, Fernández-Salazar L, Calvo C, Chirdo FG, Garrote JA, Arranz E - Nutrients (2015)

Bottom Line: The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile.In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status.A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.

View Article: PubMed Central - PubMed

Affiliation: Mucosal Immunology Lab, IBGM, University of Valladolid-CSIC, Sanz y Forés 3, 47003 Valladolid, Spain. emontalvillo@gmail.com.

ABSTRACT
Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.

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Increased duodenal Vα24-Jα18 mRNA expression in untreated and treated celiac disease patients. Expression levels of Vα24-Jα18 mRNA in duodenal biopsies indicated by the ratio Vα24-Jα18/βactin in arbitrary units (AU), in untreated Celiac Disease (uCD), Gluten Free Diet-CD patients (GFD-CD), inflamed non-CD controls (I-controls) and non-inflamed non-CD controls (C-controls) in the Spanish population (A) and in uCD and C-controls in the Argentinian population (B). Statistically significant differences are shown (two tailed Mann-Whitney U test; Krustall-Wallis test). Horizontal bars are median values. Correlation between the degree of histological lesion (Marsh score) and the expression level of Vα24-Jα18 mRNA in CD patients. (1: Marsh 0-I, 2: Marsh II, 3: Marsh IIIa, 4: Marsh IIIb, 5: Marsh IIIc) There was an increased of Vα24-Jα18 expression and the duodenal increased level of atrophy (Spearman r = 0.063, p < 0.05). GFD-CD patients show a Marsh 0-I, uCD show duodenal atrophy Marsh II to IIIc (C).
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nutrients-07-05444-f002: Increased duodenal Vα24-Jα18 mRNA expression in untreated and treated celiac disease patients. Expression levels of Vα24-Jα18 mRNA in duodenal biopsies indicated by the ratio Vα24-Jα18/βactin in arbitrary units (AU), in untreated Celiac Disease (uCD), Gluten Free Diet-CD patients (GFD-CD), inflamed non-CD controls (I-controls) and non-inflamed non-CD controls (C-controls) in the Spanish population (A) and in uCD and C-controls in the Argentinian population (B). Statistically significant differences are shown (two tailed Mann-Whitney U test; Krustall-Wallis test). Horizontal bars are median values. Correlation between the degree of histological lesion (Marsh score) and the expression level of Vα24-Jα18 mRNA in CD patients. (1: Marsh 0-I, 2: Marsh II, 3: Marsh IIIa, 4: Marsh IIIb, 5: Marsh IIIc) There was an increased of Vα24-Jα18 expression and the duodenal increased level of atrophy (Spearman r = 0.063, p < 0.05). GFD-CD patients show a Marsh 0-I, uCD show duodenal atrophy Marsh II to IIIc (C).

Mentions: Untreated-CD patients (uCD) had increased Vα24-Jα18 mRNA levels compared to both inflamed non-CD (I-controls) (p < 0.05) and non-inflamed non-CD controls (C-controls) (p < 0.001) (Figure 2A). Gluten Free Diet-CD patients (GFD-CD) had increased Vα24-Jα18 mRNA levels compared to C-controls (p < 0.001). No differences were found between uCD and GFD-CD patients, which suggests an increased load of iNKT cells in duodenal biopsies from both groups of patients irrespectively of the disease status (Figure 2A). We also analyzed duodenal expression of Vα24-Jα18 mRNA in an independent population from Argentina. Figure 2B confirms that CD patients show increased duodenal Vα24-Jα18 mRNA levels compared to non-inflamed non-CD controls (p < 0.001), irrespectively of the origin of the samples. No statistically significant differences in Vα24-Jα18 mRNA levels were found between the Spanish and the Argentinian populations, neither within the control nor the untreated CD patient groups.


Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum.

Montalvillo E, Bernardo D, Martínez-Abad B, Allegretti Y, Fernández-Salazar L, Calvo C, Chirdo FG, Garrote JA, Arranz E - Nutrients (2015)

Increased duodenal Vα24-Jα18 mRNA expression in untreated and treated celiac disease patients. Expression levels of Vα24-Jα18 mRNA in duodenal biopsies indicated by the ratio Vα24-Jα18/βactin in arbitrary units (AU), in untreated Celiac Disease (uCD), Gluten Free Diet-CD patients (GFD-CD), inflamed non-CD controls (I-controls) and non-inflamed non-CD controls (C-controls) in the Spanish population (A) and in uCD and C-controls in the Argentinian population (B). Statistically significant differences are shown (two tailed Mann-Whitney U test; Krustall-Wallis test). Horizontal bars are median values. Correlation between the degree of histological lesion (Marsh score) and the expression level of Vα24-Jα18 mRNA in CD patients. (1: Marsh 0-I, 2: Marsh II, 3: Marsh IIIa, 4: Marsh IIIb, 5: Marsh IIIc) There was an increased of Vα24-Jα18 expression and the duodenal increased level of atrophy (Spearman r = 0.063, p < 0.05). GFD-CD patients show a Marsh 0-I, uCD show duodenal atrophy Marsh II to IIIc (C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663572&req=5

nutrients-07-05444-f002: Increased duodenal Vα24-Jα18 mRNA expression in untreated and treated celiac disease patients. Expression levels of Vα24-Jα18 mRNA in duodenal biopsies indicated by the ratio Vα24-Jα18/βactin in arbitrary units (AU), in untreated Celiac Disease (uCD), Gluten Free Diet-CD patients (GFD-CD), inflamed non-CD controls (I-controls) and non-inflamed non-CD controls (C-controls) in the Spanish population (A) and in uCD and C-controls in the Argentinian population (B). Statistically significant differences are shown (two tailed Mann-Whitney U test; Krustall-Wallis test). Horizontal bars are median values. Correlation between the degree of histological lesion (Marsh score) and the expression level of Vα24-Jα18 mRNA in CD patients. (1: Marsh 0-I, 2: Marsh II, 3: Marsh IIIa, 4: Marsh IIIb, 5: Marsh IIIc) There was an increased of Vα24-Jα18 expression and the duodenal increased level of atrophy (Spearman r = 0.063, p < 0.05). GFD-CD patients show a Marsh 0-I, uCD show duodenal atrophy Marsh II to IIIc (C).
Mentions: Untreated-CD patients (uCD) had increased Vα24-Jα18 mRNA levels compared to both inflamed non-CD (I-controls) (p < 0.05) and non-inflamed non-CD controls (C-controls) (p < 0.001) (Figure 2A). Gluten Free Diet-CD patients (GFD-CD) had increased Vα24-Jα18 mRNA levels compared to C-controls (p < 0.001). No differences were found between uCD and GFD-CD patients, which suggests an increased load of iNKT cells in duodenal biopsies from both groups of patients irrespectively of the disease status (Figure 2A). We also analyzed duodenal expression of Vα24-Jα18 mRNA in an independent population from Argentina. Figure 2B confirms that CD patients show increased duodenal Vα24-Jα18 mRNA levels compared to non-inflamed non-CD controls (p < 0.001), irrespectively of the origin of the samples. No statistically significant differences in Vα24-Jα18 mRNA levels were found between the Spanish and the Argentinian populations, neither within the control nor the untreated CD patient groups.

Bottom Line: The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile.In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status.A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.

View Article: PubMed Central - PubMed

Affiliation: Mucosal Immunology Lab, IBGM, University of Valladolid-CSIC, Sanz y Forés 3, 47003 Valladolid, Spain. emontalvillo@gmail.com.

ABSTRACT
Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.

Show MeSH
Related in: MedlinePlus