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Differential IL-13 production by small intestinal leukocytes in active coeliac disease versus refractory coeliac disease.

Gross S, van Wanrooij RL, Nijeboer P, Gelderman KA, Cillessen SA, Meijer GA, Mulder CJ, Bouma G, von Blomberg BM, Bontkes HJ - Mediators Inflamm. (2013)

Bottom Line: Secretion of the T(H)2 cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs) isolated from RCDII patients as compared to LPL from ACD patients (P = 0.05).In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients (P = 0.02).Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.

ABSTRACT
A small fraction of coeliac disease (CD) patients have persistent villous atrophy despite strict adherence to a gluten-free diet. Some of these refractory CD (RCD) patients develop a clonal expansion of lymphocytes with an aberrant phenotype, referred to as RCD type II (RCDII). Pathogenesis of active CD (ACD) has been shown to be related to gluten-specific immunity whereas the disease is no longer gluten driven in RCD. We therefore hypothesized that the immune response is differentially regulated by cytokines in ACD versus RCDII and investigated mucosal cytokine release after polyclonal stimulation of isolated mucosal lymphocytes. Secretion of the T(H)2 cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs) isolated from RCDII patients as compared to LPL from ACD patients (P = 0.05). In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients (P = 0.02). IL-13 secretion correlated with other T(H)2 as well as T(H)1 cytokines but not with IL-10 secretion. Overall, the cytokine production pattern of LPL in RCDII showed more similarities with LPL isolated from GFD patients than from ACD patients. Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.

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Related in: MedlinePlus

Correlation between (a) IL-13 and IL-17A, (b) TNFα, (c) IL-5, (d) IFNγ and (e) IL-10 production in all groups. Correlations were tested with a two-sided Pearson correlation.
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fig3: Correlation between (a) IL-13 and IL-17A, (b) TNFα, (c) IL-5, (d) IFNγ and (e) IL-10 production in all groups. Correlations were tested with a two-sided Pearson correlation.

Mentions: In contrast to LPS, stimulation of LPL with PMA/ionomycin resulted in detectable cytokine levels. RCDII patients who were treated within 6 weeks before the biopsy was taken appeared not to be different in terms of cytokine production from patients who were treated more than 6 weeks before the biopsy was taken (Figure 2 and Table 2). However, levels of most cytokines (IFNγ, TNFα, IL-13, and IL-17A) tended to be the highest in patients with persisting villous atrophy (Figure 2, closed symbols). Similar to the IEL results, IFNγ production by LPL was comparable between ACD and RCDII patients and IFNγ production was not reduced in GFD patients compared to ACD (Figure 2(a)). IL-13 responses were higher in RCDII when compared to ACD patients but were also higher in GFD as compared to ACD (Figure 2(c)). Since IL-13 production was significantly increased in RCDII patients as compared to ACD patients, we analysed the coexpression of IL-13 and the other cytokines by calculating correlation coefficients for all IL-13 cytokine pairs. IL-13 release correlated the strongest with IL-17A and TNF (r = 0.80 and r = 0.73, resp.; both P < 0.001; Figures 3(a) and 3(b)). Weaker correlations were observed with IL-5 and IFNγ (r = 0.63, P = 0.003 and r = 0.45, P = 0.04, resp.; Figures 3(c) and 3(d)), while there was no significant correlation between IL-13 and IL-10 (r = 0.38, P = 0.10; Figure 3(e)).


Differential IL-13 production by small intestinal leukocytes in active coeliac disease versus refractory coeliac disease.

Gross S, van Wanrooij RL, Nijeboer P, Gelderman KA, Cillessen SA, Meijer GA, Mulder CJ, Bouma G, von Blomberg BM, Bontkes HJ - Mediators Inflamm. (2013)

Correlation between (a) IL-13 and IL-17A, (b) TNFα, (c) IL-5, (d) IFNγ and (e) IL-10 production in all groups. Correlations were tested with a two-sided Pearson correlation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3649694&req=5

fig3: Correlation between (a) IL-13 and IL-17A, (b) TNFα, (c) IL-5, (d) IFNγ and (e) IL-10 production in all groups. Correlations were tested with a two-sided Pearson correlation.
Mentions: In contrast to LPS, stimulation of LPL with PMA/ionomycin resulted in detectable cytokine levels. RCDII patients who were treated within 6 weeks before the biopsy was taken appeared not to be different in terms of cytokine production from patients who were treated more than 6 weeks before the biopsy was taken (Figure 2 and Table 2). However, levels of most cytokines (IFNγ, TNFα, IL-13, and IL-17A) tended to be the highest in patients with persisting villous atrophy (Figure 2, closed symbols). Similar to the IEL results, IFNγ production by LPL was comparable between ACD and RCDII patients and IFNγ production was not reduced in GFD patients compared to ACD (Figure 2(a)). IL-13 responses were higher in RCDII when compared to ACD patients but were also higher in GFD as compared to ACD (Figure 2(c)). Since IL-13 production was significantly increased in RCDII patients as compared to ACD patients, we analysed the coexpression of IL-13 and the other cytokines by calculating correlation coefficients for all IL-13 cytokine pairs. IL-13 release correlated the strongest with IL-17A and TNF (r = 0.80 and r = 0.73, resp.; both P < 0.001; Figures 3(a) and 3(b)). Weaker correlations were observed with IL-5 and IFNγ (r = 0.63, P = 0.003 and r = 0.45, P = 0.04, resp.; Figures 3(c) and 3(d)), while there was no significant correlation between IL-13 and IL-10 (r = 0.38, P = 0.10; Figure 3(e)).

Bottom Line: Secretion of the T(H)2 cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs) isolated from RCDII patients as compared to LPL from ACD patients (P = 0.05).In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients (P = 0.02).Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.

ABSTRACT
A small fraction of coeliac disease (CD) patients have persistent villous atrophy despite strict adherence to a gluten-free diet. Some of these refractory CD (RCD) patients develop a clonal expansion of lymphocytes with an aberrant phenotype, referred to as RCD type II (RCDII). Pathogenesis of active CD (ACD) has been shown to be related to gluten-specific immunity whereas the disease is no longer gluten driven in RCD. We therefore hypothesized that the immune response is differentially regulated by cytokines in ACD versus RCDII and investigated mucosal cytokine release after polyclonal stimulation of isolated mucosal lymphocytes. Secretion of the T(H)2 cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs) isolated from RCDII patients as compared to LPL from ACD patients (P = 0.05). In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients (P = 0.02). IL-13 secretion correlated with other T(H)2 as well as T(H)1 cytokines but not with IL-10 secretion. Overall, the cytokine production pattern of LPL in RCDII showed more similarities with LPL isolated from GFD patients than from ACD patients. Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.

Show MeSH
Related in: MedlinePlus