Macrophages inhibit and enhance endometriosis depending on their origin.
Macrophages inhibit and enhance endometriosis depending on their origin.
复制标题
DOI：
10.1073/pnas.2013776118
复制
发表时间：
2021-02-09
影响因子：
11.1
通讯作者：
Greaves E
中科院分区：
文献类型：
--
作者：
Hogg C;Panir K;Dhami P;Rosser M;Mack M;Soong D;Pollard JW;Jenkins SJ;Horne AW;Greaves E
子宫内膜异位症是一种慢性、不可治愈的炎症性疾病，影响全球1.9亿女性。称为巨噬细胞的免疫细胞参与促进子宫内膜异位症。宏程序有不同的起源，它们的起源可以决定功能。在这项研究中，我们证明，子宫内膜异位症病变驻留巨噬细胞来自子宫内膜（子宫内膜），腹腔（腹膜）腔，并招募骨髓前体细胞（单核细胞）。子宫内膜异位症触发单核细胞的持续募集，单核细胞分化成巨噬细胞，巨噬细胞不同于通常存在于腹腔内的巨噬细胞。通过消耗不同的人群，我们证明了子宫内膜巨噬细胞是“促子宫内膜异位症”，而单核细胞来源的腹腔巨噬细胞是“抗子宫内膜异位症”的作用，以保护腔病变的建立。在未来，基于免疫的疗法可能允许靶向促疾病巨噬细胞和/或利用抗子宫内膜异位症巨噬细胞治疗子宫内膜异位症。巨噬细胞与子宫内膜异位症的病理生理密切相关，子宫内膜异位症是一种慢性炎症性疾病，其特征是子宫外的血管样组织（病变）生长。通过结合遗传学和药理学的单核细胞和巨噬细胞耗竭策略，我们确定了诱导子宫内膜异位症小鼠模型中巨噬细胞的个体发育和功能。我们证明，病变驻留巨噬细胞来自在位子宫内膜组织，浸润大腹腔巨噬细胞（LpM）和单核细胞。此外，我们发现子宫内膜异位症引发单核细胞的持续募集和CCR 2 + LpM的扩增。在位子宫内膜巨噬细胞的耗竭导致较小的子宫内膜异位症病变，而单核细胞募集的组成性抑制显着减少腹腔巨噬细胞群，并增加病变的数量。重新编程腹膜巨噬细胞的个体发育，使得胚胎来源的LpM被单核细胞来源的LpM取代，从而减少了发生的病变的数量。我们提出了一个假定的模型，即子宫内膜巨噬细胞是“促子宫内膜异位症”，而新招募的单核细胞衍生的巨噬细胞，可能在LpM的形式，是“抗子宫内膜异位症”。这些观察结果突出了单核细胞衍生的巨噬细胞在限制疾病进展中的重要性。
Endometriosis is a chronic, incurable inflammatory disorder impacting 190 million women worldwide. Immune cells called macrophages are implicated in promoting endometriosis. Macrophages have different origins and their origin can dictate function. In this study we demonstrate that endometriotic lesion-resident macrophages are derived from the uterine lining (endometrium), the abdominal (peritoneal) cavity, and recruited bone-marrow precursors (monocytes). Endometriosis triggers continuous recruitment of monocytes that differentiate into macrophages that differ from those usually present within the peritoneal cavity. By depleting different populations, we demonstrate that endometrial macrophages are “proendometriosis” while monocyte-derived peritoneal macrophages are “antiendometriosis” acting to protect the cavity from lesion establishment. In the future, immune-based therapies may allow targeting of prodisease macrophages and/or harnessing of antiendometriosis macrophages in endometriosis. Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increases the number of lesions. Reprogramming the ontogeny of peritoneal macrophages such that embryo-derived LpM are replaced by monocyte-derived LpM decreases the number of lesions that develop. We propose a putative model whereby endometrial macrophages are “proendometriosis” while newly recruited monocyte-derived macrophages, possibly in LpM form, are “antiendometriosis.” These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.
登录
查看更多内容
影响因子：
20.3
作者：
Gautier, Emmanuel L.;Ivanov, Stoyan;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
影响因子：
64.5
作者：
Lavin Y;Winter D;Blecher-Gonen R;David E;Keren-Shaul H;Merad M;Jung S;Amit I
通讯作者：
Amit I
影响因子：
4.6
作者：
Cousins FL;Kirkwood PM;Saunders PT;Gibson DA
通讯作者：
Gibson DA
影响因子：
6
作者：
Greaves, Erin;Ternp, Julia;Saunders, Philippa T. K.
通讯作者：
Saunders, Philippa T. K.
通过 Ms4a3 表达历史追踪单核细胞衍生细胞的命运图谱
影响因子：
64.5
作者：
Liu, Zhaoyuan;Gu, Yaqi;Ginhoux, Florent
通讯作者：
Ginhoux, Florent