Deletion of the G2A receptor fails to attenuate experimental autoimmune encephalomyelitis.
Deletion of the G2A receptor fails to attenuate experimental autoimmune encephalomyelitis.
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DOI：
10.1016/j.jneuroim.2008.11.008
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发表时间：
2009-02-15
影响因子：
3.3
通讯作者：
Kabarowski, Janusz H. S.
中科院分区：
文献类型：
--
作者：
Osmers, Inga;Smith, Sherry S.;Parks, Brian W.;Yu, Shaohua;Srivastava, Roshni;Wohler, Jillian E.;Barnum, Scott R.;Kabarowski, Janusz H. S.
溶血磷脂酰胆碱（LPC）是炎症过程中由磷脂酶A2水解作用产生的一种趋化溶脂。LPC通过激活G蛋白偶联受体G2A，在体外刺激T细胞趋化。这导致了G2A有助于T细胞募集到炎症部位，从而促进慢性炎症性自身免疫性疾病，这些疾病与自身抗原特异性效应T细胞的产生和随后的组织浸润有关。然而，一项研究表明，G2A可能负性调节T细胞对抗原受体的增殖反应，从而通过减少自身反应性T细胞的产生来减弱自身免疫。为了解决这些G2A介导的作用在T细胞介导的自身免疫性疾病的病理生理学中的相对贡献，我们研究了G2A失活对小鼠实验性自身免疫性脑脊髓炎（EAE）的发病和严重程度的影响，EAE是多发性硬化症（MS）的一种模型。野生型（G2A+/+）和G2A缺陷型（G2A-/-） C57BL/6J小鼠在MOG35-55肽免疫后表现出相似的发病率和发病。G2A-/-小鼠的疾病严重程度仅中度降低。在免疫MOG35-55的G2A+/+和G2A-/-小鼠的次级淋巴器官中产生了相似数量的MOG35-55特异性T细胞。在G2A+/+和G2A-/-小鼠的脊髓中检测到相当数量的T细胞。我们的结论是，G2A的抗增殖和趋化功能在体内没有表现出来，因此G2A的治疗靶向不太可能对MS的治疗有益。
Lysophosphatidylcholine (LPC) is a chemotactic lysolipid produced during inflammation by the hydrolytic action of phospholipase A2 enzymes. LPC stimulates chemotaxis of T cells in vitro through activation of the G protein-coupled receptor, G2A. This has led to the proposition that G2A contributes to the recruitment of T cells to sites of inflammation and thus promotes chronic inflammatory autoimmune diseases associated with the generation and subsequent tissue infiltration of auto-antigen-specific effector T cells. However, one study suggests that G2A may negatively regulate T cell proliferative responses to antigen receptor engagement and thereby attenuates autoimmunity by reducing the generation of autoreactive T cells. To address the relative contribution of these G2A-mediated effects to the pathophysiology of T cell-mediated autoimmune disease, we examined the impact of G2A inactivation on the onset and severity of murine experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Wild type (G2A+/+) and G2A-deficient (G2A-/-) C57BL/6J mice exhibited a similar incidence and onset of disease following immunization with MOG35-55 peptide. Disease severity was only moderately reduced in G2A-/- mice. Similar numbers of MOG35-55 specific T cells were generated in secondary lymphoid organs of MOG35-55-immunized G2A+/+ and G2A-/- mice. Comparable numbers of T cells were detected in spinal cords of G2A+/+ and G2A-/- mice. We conclude that the proposed anti-proliferative and chemotactic functions of G2A are not manifested in vivo and therefore therapeutic targeting of G2A is unlikely to be beneficial in the treatment of MS.
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影响因子：
3.6
作者：
Ebert, LA;Schaerli, P;Moser, B
通讯作者：
Moser, B
DOI：
10.1161/01.atv.0000246774.02426.71
发表时间：
2006-12-01
影响因子：
8.7
作者：
Parks, Brian W.;Lusis, Aldons J.;Kabarowski, Janusz H. S.
通讯作者：
Kabarowski, Janusz H. S.
DOI：
10.1073/pnas.2536801100
发表时间：
2004-01-06
影响因子：
11.1
作者：
Radu, CG;Yang, LV;Witte, ON
通讯作者：
Witte, ON
影响因子：
16.2
作者：
Kalyvas, A;David, S
通讯作者：
David, S
影响因子：
3.3
作者：
Adams, Jillian E.;Webb, Matthew S.;Barnum, Scott R.
通讯作者：
Barnum, Scott R.