Transglutaminase 2 expressed in mast cells recruited into skin or bone marrow induces the development of pediatric mastocytosis. Issue 5 (August 2015)

• Record Type: Journal Article
• Authors: Ahn, Young Min; Hong, Gwan Ui; Kim, Sang Hoon; Lee, Ho Jung; Baek, Hey Sung; Kim, Myung Nam; Park, Kui Young; Ro, Jai Youl
• Is Part Of: Pediatric allergy and immunology. Volume 26:Issue 5(2015)
• Page Start: 438
• Page End: 445
• Publication Date: 2015-08
• Subjects: Allergy in children -- Periodicals; Immunologic diseases in children -- Periodicals; 617
• DOI: 10.1111/pai.12403
• Languages: English
• ISSNs: 0905-6157

Abstract

<abstract abstract-type="main" id="pai12403-abs-0001"> <title>Abstract</title> <sec id="pai12403-sec-0001" sec-type="section"> <title>Background</title> <p>Mastocytosis is characterized by a pathological increase in mast cells in organs such as skin and bone marrow. Transglutaminase 2 (TG2) expressed in mast cells contributes to allergic diseases, but its role in mastocytosis has not been investigated. This study aimed to investigate whether TG2 contributes to pediatric mastocytosis.</p> </sec> <sec id="pai12403-sec-0002" sec-type="section"> <title>Methods</title> <p>Serum, various skin tissues or bone marrow (BM) biopsy and aspirates were obtained from pediatric normal control or patients with indolent systemic mastocytosis (SM), mastocytoma, and urticaria pigmentosa (UP). Tryptase, individual cytokines, leukotriene C<sub>4</sub> (LTC<sub>4</sub>), and TG2 activity in the serum were determined by enzyme‐linked immunosorbent assay, mast cell population by May–Grünwald–Giemsa, CD 117 by immunofluorescence, cell surface molecules by Western blot, and colocalization of c‐kit and TG2 or IL‐10‐expressing cells, CD25, and FOXP3 by immunohistochemistry.</p> </sec> <sec id="pai12403-sec-0003" sec-type="section"> <title>Results</title> <p>Infiltration of CD25<sup>+</sup>CD117<sup>+</sup>CD2<sup>‐</sup> mast cells into BM and scalp/trunk/ear dermis; expression of FcεRI, tryptase, c‐kit, FOXP3, CCL2/CCR2, and vascular cell adhesion molecule‐1; and colocalization of c‐kit and TG2 were enhanced in patient′s skin tissues or BM, particularly SM, but colocalization of c‐kit and IL‐10‐expressing cells was decreased vs. normal tissues. Amounts of LTC<sub>4</sub> and inflammatory cytokines, expression of tryptase or TG2 activity were increased in patient's serum, BM aspirates, or ear/scalp skin tissues, respectively, vs. normal persons, but IL‐10 level was decreased.</p> </sec> <sec id="pai12403-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The data suggest that mast cells, recruited in the skin and BM by CCL2/CCR, may induce the development of pediatric mastocytosis through reducing IL‐10 due to upregulating TG2 activity via transcription factor nuclear factor‐κB. Thus, TG2 may be used in diagnosis of pediatric mastocytosis, particularly SM.</p> </sec> </abstract>