Research Article: Expression of intelectin-1 in bronchial epithelial cells of asthma is correlated with T-helper 2 (Type-2) related parameters and its function

Date Published: August 1, 2017

Publisher: BioMed Central

Author(s): Taiji Watanabe, Kazuyuki Chibana, Taichi Shiobara, Rinna Tei, Ryosuke Koike, Yusuke Nakamura, Ryo Arai, Yukiko Horigane, Yasuo Shimizu, Akihiro Takemasa, Takeshi Fukuda, Sally E. Wenzel, Yoshiki Ishii.


Intelectin-1 (ITLN-1) is secreted by intestinal goblet cells and detectable in blood. Its expression is increased in IL-13-overexpressing mouse airways. However, its expression and function in human airways is poorly understood.

Distal and proximal bronchial epithelial cells (BECs) were isolated from bronchoscopic brushings of disease control (D-CON), COPD, inhaled corticosteroid-treated asthma (ST-Asthma) and inhaled corticosteroid-naïve asthma (SN-Asthma) patients. ITLN-1 mRNA expression in freshly isolated BECs, primary cultured BECs with or without IL-13 and inhibition effects of mometasone furoate (MF) were investigated by quantitative real-time PCR (qPCR). Correlations between ITLN-1 mRNA and Type-2 related parameters (e.g. FeNO, IgE, iNOS, CCL26, periostin and DPP4 mRNA) were analyzed. ITLN-1 protein distribution in asthmatic airway tissue was assessed by immunohistochemistry. Bronchial alveolar lavage (BAL) and serum ITLN-1 protein were measured by ELISA. The effect of recombinant human (rh) ITLN-1 on stimulated production of CXCL10 and phospho(p)-STAT1 expression examined in lung fibroblasts.

ITLN-1 mRNA was expressed in freshly isolated BECs and was correlated with Type-2 related parameters. ITLN-1 protein was increased in goblet cells in SN-Asthmatics and increased in SN-Asthmatic BAL fluid. There were no any differences in serum ITLN-1 concentration between ST and SN-Asthma. IL-13 enhanced ITLN-1 expression and inhibited by MF from BECs in vitro, while rhITLN-1 inhibited CXCL10 production and p-STAT1 expression in HFL-1 cells.

ITLN-1 is induced by IL-13 and expressed mainly in goblet cells in untreated asthma where its levels correlate with known Type-2 related parameters. Further, ITLN-1 inhibits Type-1 chemokine expression.

The online version of this article (doi:10.1186/s13223-017-0207-8) contains supplementary material, which is available to authorized users.

Partial Text

Asthma affects nearly 300 million people worldwide but is a heterogeneous disorder comprised of different inflammatory characteristics. Type-2 cytokines (specifically, interleukin (IL)-4, IL-5, and IL-13) are known to play a substantial pathobiological role in many cases. These cytokines, including IL-13 contribute to a Type-2-high molecular asthma phenotype in about 50% of patients with asthma, and are widely believed to play important roles in asthma pathophysiology [1–7]. Furthermore, IL-13-induced periostin [8] and DPP4 can be measured in peripheral blood and are used as biomarkers to predict the efficacy of anti-IL-13 antibodies in human asthma patients [9–11].

In this study, ITLN-1 was induced by IL-13 and mainly expressed in goblet cells of the distal and proximal airways in SN-Asthma patients. In the SN-Asthma group, ITLN-1 mRNA correlated with FeNO, IgE, iNOS, CCL26, periostin and DPP4 mRNA, all Type-2 related parameters. Finally, our results suggest that ITLN-1 might lead to Type-2-bias by attenuating IFN-γ signaling.

ITLN-1 is expressed in untreated asthmatic bronchial epithelial cells, particularly in goblet cells, in association with Type-2 related parameters. However, it appears to be suppressed by corticosteroids in vivo, and epithelial ITLN-1 does not appear to contribute substantially to serum levels, making it unsuitable as a Type-2 asthma biomarker. Its true role in asthma requires further study, perhaps in association with lactoferrin, but it has the potential to further skew inflammation away from Type-1 and towards a Type-2 process.




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