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シェーグレン症候群唾液腺細胞死とHTLV-Iの関与


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Title: シェーグレン症候群唾液腺細胞死とHTLV-Iの関与
Other Titles: Cell death of salivary gland epithelial cells and involvement of HTLV-I in Sjögren's syndrome
Authors: 中村, 英樹
Authors (alternative): Nakamura, Hideki
Issue Date: 30-Jun-2014
Publisher: 日本臨床免疫学会 / The Japan Society for Clinical Immunology
Citation: 日本臨床免疫学会会誌, 37(3), pp.117-124; 2014
Abstract: シェーグレン症候群(SS)唾液腺慢性炎症の原因として,唾液腺上皮細胞の細胞死が挙げられる.Fas/Fas ligandや細胞障害性顆粒の関与が知られているが,TRAILによるミトコンドリア経路を介したアポトーシスの関与もみられ,自然免疫系では,TLR3リガンド刺激によりアポトーシス誘導がおこる.また抗アポトーシス分子発現と唾液腺より分泌されるepidermal growth factorが密接に関与していることも明らかとなった.一方,ウイルス感染とSSとの関与も以前より示唆されているが,疫学的にはHTLV-IとSSとの関連が明らかとなっており,HTLV-I関連脊髄症(HAM)においてはSS合併が高頻度である.また,抗HTLV-I陽性SS群では唾液腺破壊が生じにくく,これに異所性二次濾胞(GC)の陽性率が関与していた.HTLV-I感染細胞株HCT-5と,SS患者由来の唾液腺上皮細胞の共培養を行った.共培養上清のサイトカインアレイでは,細胞接着・遊走に関わる分子の経時的増加が観察された.また,共培養時のライセートのアポトーシスアレイでは,FasやチトクロームCなど細胞死を誘導する分子と共にHSP27など抗アポトーシス分子の発現亢進も観察されたが,この間アポトーシス増加は観察されなかった.現在これらvitroの系でHTLV-IとSS唾液腺の関連を検討中である. / Chronic sialadenitis in Sjögren's syndrome (SS) is associated with cell death induced by Fas or cytotoxic granules. Furthermore, tumor necrosis factor-related apoptosis inducing ligand or toll-like receptor3 are known to induce apoptosis in the salivary gland epithelial cells (SGECs) derived from patients with SS. Anti-apoptotic molecules that are closely related to epidermal growth factor are known to inhibit apoptosis. Epidemiologically, high prevalence of HTLV-I in primary Sjögren's syndrome (SS) patients has been found in an endemic area. However, by comparison of radiographic imaging with mononuclear cells (MNCs) infiltration of LSGs, we have found that there are significantly fewer abnormalities determined by sialography in HTLV-I-seropositive SS patients in comparison with HTLV-I-seronegative SS patients irrespective of similar grade of MNCs infiltration. In HTLV-I-seropositive SS patients, low frequency of salivary gland destruction was observed and this phenomenon was associated with frequency of the ectopic germinal center (GC). Then, we show cytokine profile in culture supernatant of salivary gland epithelial cells co-cultured with HCT-5 established from spinal fluid of patients with HAM. Up-regulation of adhesion molecule or migration factor was observed in culture supernatant. On the other hand, co-cultured cell lysate showed apoptotic and anti-apoptotic molecules without increase of apoptosis. Detailed molecular mechanisms in these processes are under study.
Keywords: Sjögren's syndrome / apoptosis / HTLV-I / germinal center
URI: http://hdl.handle.net/10069/34720
ISSN: 09114300
DOI: 10.2177/jsci.37.117
Rights: © 2014 日本臨床免疫学会
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/34720

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