Activated complement component 3 (C3) is required for ultraviolet induction of immunosuppression and antigenic tolerance.
Activated complement component 3 (C3) is required for ultraviolet induction of immunosuppression and antigenic tolerance.
复制标题
DOI：
10.1084/jem.187.7.1133
复制
发表时间：
1998-04-06
影响因子：
15.3
通讯作者：
Cooper, KD
中科院分区：
文献类型：
--
作者：
Hammerberg, C;Katiyar, SK;Carroll, MC;Cooper, KD
补体成分3（C3）是先天免疫的关键调节剂，也可以在同源免疫的调节中发挥作用，例如接触敏感性反应。由于紫外线（UV）辐射也会激活皮肤中的C3，因此我们确定了当通过UVB暴露的皮肤应用接触敏化剂时导致的免疫抑制状态是否需要C3的存在和激活。通过使用C3缺陷小鼠、阻断C3裂解为C3b以及可溶性补体受体1（sCR1）加速iC3b降解来解决该问题。这两个C3调制系统完全逆转了未能诱导接触敏感性反应二硝基氟苯（DNFB）后，在紫外线暴露部位的初级致敏，以及免疫耐受的第二DNFB免疫通过正常皮肤。用sCR1治疗减少了CD 11b+白细胞向UV照射皮肤的表皮和真皮的浸润，但没有逆转UV诱导的表皮II类MHC+ CD 11blo朗格汉斯细胞的耗竭。这些数据与先前显示通过体内抗CD11b治疗消除局部诱导的UV免疫抑制的结果一起，提示了一种新的机制，通过该机制，白细胞β2整联蛋白CD11b通过UV暴露皮肤中C3活化形成的iC3b分子连接，修饰皮肤CD11b+细胞，使得皮肤抗原呈递细胞不能在初次免疫应答中敏化，而是主动诱导抗原耐受性。
Complement component 3 (C3), a critical regulator of innate immunity, may also play a role in the regulation of cognate immunity, such as contact sensitivity responses. Because ultraviolet (UV) radiation also activates C3 in the skin, we determined whether the immunosuppressed state that results when a contact sensitizer is applied through UVB-exposed skin requires the presence and activation of C3. This question was addressed through the use of C3-deficient mice, blockade of C3 cleavage to C3b, and accelerated degradation of iC3b by soluble complement receptor 1 (sCR1). Both C3-modulated systems totally reversed the failure to induce a contact sensitivity response to dinitrofluorobenzene (DNFB) upon primary sensitization at the UV-exposed site, as well as immunologic tolerance to a second DNFB immunization through normal skin. Treatment with sCR1 reduced the infiltration of CD11b+ leukocytes into the epidermis and dermis of UV-irradiated skin but did not reverse the UV-induced depletion of epidermal class II MHC+CD11blo Langerhans cells. These data, taken together with previous results showing abrogation of locally induced UV immunosuppression by in vivo anti-CD11b treatment, suggest a novel mechanism by which ligation of the leukocyte β2 integrin, CD11b, by iC3b molecules formed from C3 activation in UV-exposed skin, modifies cutaneous CD11b+ cells such that skin antigen-presenting cells are unable to sensitize in a primary immune response, but actively induce antigenic tolerance.
登录
查看更多内容
影响因子：
7.8
作者：
Graham, I L;Anderson, D C;Holers, V M;Brown, E J
通讯作者：
Brown, E J
影响因子：
6.5
作者：
BASSETSEGUIN, N;PORNEUF, M;GUILHOU, JJ
通讯作者：
GUILHOU, JJ
影响因子：
15.9
作者：
DOVEZENSKI, N;BILLETTA, R;GIGLI, I
通讯作者：
GIGLI, I
影响因子：
15.3
作者：
Marth, T;Kelsall, BL
通讯作者：
Kelsall, BL
影响因子：
6.5
作者：
Hammerberg, C;Duraiswamy, N;Cooper, KD
通讯作者：
Cooper, KD