Pathological analysis of skin fibrosis, focused on type 2 innate immune lymphoid cells
| Project/Area Number |
24659520
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Chiba University |
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Principal Investigator |
KAMBE Naotomo 千葉大学, 医学研究院, 准教授 (50335254)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAE Susumu 東京大学, 医科 学研究所, 准教授 (60450409)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 皮膚炎症・再生学 / 皮膚硬化性病変 / ＩＬ-33 |
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| Research Abstract |
We have studied the mechanism of cryopyrin-associated periodicsyndrome (CAPS), in which an active mutant of NLRP3 spontaneously forms inflammasome andinduces hyper-production of IL-1β. This study led us to focus on the pivotal role of IL-1 in skindiseases. Recently, people pay attention to another IL-1 family molecule, IL-33, because IL-33released from damaged cells in inflammation is critically involved in inflammatory response by aproduction of Th2 cytokines and a degranulation of mast cells. In addition, IL-33 induces a largeamount of Th2 cytokine production from innate lymphoid cells (ILCs). ILCs are newly identifiedlymphoid lineage cells, keep haematopoietic stem cell markers and are present in the mesentericfat-associated lymphoid clusters.
Interestingly, the structure of mesenteric fat-associated lymphoid clusters shares thesimilar feature with that of aggregated clusters of lymphoid cells in subcutaneous fat in localizedscleroderma. Also serum IL-33 is reported to be elevated in scleroderma and serum levels of IL-33is well correlated with the severity of cutaneous sclerosis in scleroderma. Therefore, we studied therole of IL-33 in bleomycin-induced scleroderma murine model by comparing the effect in IL-33deficient mice and wild type mice.
Six weeks after bleomycin-treatment, we obtained localized cutaneous sclerosisaccompanied with increased skin fibrosis in wild type mice. However, lymphoid cell infiltrationwas not observed in the skin lesion. Unfortunately, the cutaneous sclerosis including histologicalfeatures in IL-33 deficient mice was almost identical to that in wild type mice. We concluded from these results that we should verify the cutaneous role of IL-33 by focusing on Th2 immuneresponse, and now we are establishing such a model to confirm it.
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Report
(2 results)
Research Products
(22 results)
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[Journal Article] ST2 Requires Th2-, but Not Th17-, Type Airway Inflammation in Epicutaneously Antigen-Sensitized Mice2012
Author(s)
Morita H, Arae K, Ohno T, Kajiwara N, Oboki, K, Matsuda A, Suto H, Okumura K, Sudo K, Takahashi T, Matsumoto K, Nakae, S
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Journal Title
Allergology International
Volume: 61
Issue: 2
Pages: 265-273
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed
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[Journal Article] Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma2012
Author(s)
Suzukawa M, Morita H, Nambu A, Arae K, Shimura E, Shibui A, Yamaguchi S, Suzukawa K, Nakanishi W, Oboki K, Kajiwara N Ohno T, Ishii A, Korner H, Cua DJ, Suto H, Yoshimoto T, Iwakura Y, Yamasoba T, Ohta K, Sudo K, Saito H, Okumura K, Broide DH, Matsumoto K, Nakae S
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Journal Title
J Immunol
Volume: 189
Pages: 3641-52
Related Report
Peer Reviewed
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