IL-34 deficiency impairs FOXP3(+) Treg function in a model of autoimmune colitis and decreases immune tolerance homeostasis.
IL-34 deficiency impairs FOXP3(+) Treg function in a model of autoimmune colitis and decreases immune tolerance homeostasis.
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DOI：
10.1002/ctm2.988
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发表时间：
2022-08
影响因子：
10.6
通讯作者：
Guillonneau, Carole
中科院分区：
文献类型：
--
作者：
Freuchet, Antoine;Salama, Apolline;Bezie, Severine;Tesson, Laurent;Remy, Severine;Humeau, Romain;Regue, Hadrien;Serazin, Celine;Flippe, Lea;Peterson, Part;Vimond, Nadege;Usal, Claire;Menoret, Severine;Heslan, Jean-Marie;Duteille, Franck;Blanchard, Frederic;Giral, Magali;Colonna, Marco;Anegon, Ignacio;Guillonneau, Carole
免疫稳态需要具有稳定表型的功能完备的treg来控制自身免疫。虽然IL - 34是一种细胞因子，最初被描述为主要参与单核细胞的存活和分化，但我们最近在移植耐受大鼠模型中通过CD8+ treg表达，并在人类健康个体中通过激活FOXP3+ CD4+和CD8+ treg表达。然而，它在自身免疫中的作用和在人类疾病中的潜力仍有待确定。我们产生了Il34−/−大鼠，并使用Il34−/−大鼠和小鼠，我们研究了它们在炎症条件下的表型。使用IL - 34−/−大鼠，我们进一步分析了IL - 34表达缺失对CD4+ Tregs抑制功能的影响。我们研究了IL - 34在人类疾病中预防人源化免疫缺陷NSG小鼠异种GVHD和人皮异体移植排斥反应的潜力。最后，利用生物收集的优势，我们研究了血清中IL - 34的存在与肾移植排斥反应之间的关系。在这里，我们报道了IL - 34在IL - 34 - / -大鼠和小鼠中缺乏表达导致不稳定的免疫表型，产生多种自身抗体，在炎症条件下加剧，增加了IL - 34 - / -动物对DSS -和TNBS -结肠炎的易感性。此外，我们发现，与Il34 +/+ CD4+ Tregs相比，Il34−/−CD4+ Tregs在保护Il2rg−/−大鼠免受病原细胞转移引起的消耗性疾病方面具有明显的无能。我们还发现IL - 34治疗延迟了小鼠的EAE，延迟了人源化免疫缺陷NSG小鼠的GVHD和人皮肤同种异体移植排斥反应。最后，我们发现血清中IL - 34的存在与肾移植患者较长的无排斥期有关。总之，我们的数据强调了IL - 34对免疫稳态和CD4+ treg抑制功能的关键必要性。我们的数据还显示了IL - 34在人体移植和自身免疫中的治疗潜力。在IL - 34−/−大鼠和小鼠中缺乏IL - 34的表达会导致不稳定的免疫表型，在炎症条件下产生多种自身抗体并加剧免疫病理。Il34−/−CD4+ Tregs不能保护Il2rg−/−大鼠免受致病细胞转移引起的结肠炎。IL - 34治疗延迟了小鼠EAE，以及免疫人源化免疫缺陷NSG小鼠的急性GVHD和人皮肤同种异体移植排斥反应。IL - 34缺乏在稳定状态下对挑战的影响及其作为治疗工具的使用。
Immune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL‐34 is a cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently described its expression by CD8+ Tregs in a rat model of transplantation tolerance and by activated FOXP3+ CD4+ and CD8+ Tregs in human healthy individuals. However, its role in autoimmunity and potential in human diseases remains to be determined. We generated Il34 −/− rats and using both Il34 −/− rats and mice, we investigated their phenotype under inflammatory conditions. Using Il34 −/− rats, we further analyzed the impact of the absence of expression of IL‐34 for CD4+ Tregs suppressive function. We investigated the potential of IL‐34 in human disease to prevent xenogeneic GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, taking advantage of a biocollection, we investigated the correlation between presence of IL‐34 in the serum and kidney transplant rejection. Here we report that the absence of expression of IL‐34 in Il34 −/− rats and mice leads to an unstable immune phenotype, with production of multiple auto‐antibodies, exacerbated under inflammatory conditions with increased susceptibility to DSS‐ and TNBS‐colitis in Il34 −/− animals. Moreover, we revealed the striking inability of Il34 −/− CD4+ Tregs to protect Il2rg−/− rats from a wasting disease induced by transfer of pathogenic cells, in contrast to Il34 +/+ CD4+ Tregs. We also showed that IL‐34 treatment delayed EAE in mice as well as GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, we show that presence of IL‐34 in the serum is associated with a longer rejection‐free period in kidney transplanted patients. Altogether, our data emphasize on the crucial necessity of IL‐34 for immune homeostasis and for CD4+ Tregs suppressive function. Our data also shows the therapeutic potential of IL‐34 in human transplantation and auto‐immunity. Absence of expression of IL‐34 in Il34−/− rats and mice leads to an unstable immune phenotype, with a production of multiple auto‐antibodies and exacerbated immune pathology under inflammatory conditions. Il34−/− CD4+ Tregs are unable to protect Il2rg−/− rats from colitis induced by transfer of pathogenic cells. IL‐34 treatment delayed EAE in mice, as well as acute GVHD and human skin allograft rejection in immune‐humanized immunodeficient NSG mice. The impact of an IL‐34 deficiency at steady state, upon challenges and its use as a therapeutic tool.
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影响因子：
3.8
作者：
Kotlarz, Agnieszka;Tukaj, Stefan;Krzewski, Konrad;Brycka, Elzbieta;Lipinska, Barbara
通讯作者：
Lipinska, Barbara
危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
影响因子：
8.8
作者：
Ehx, Gregory;Ritacco, Caroline;Baron, Frederic
通讯作者：
Baron, Frederic
影响因子：
15.9
作者：
Guillonneau, Carole;Hill, Marcelo;Anegon, Ignacio
通讯作者：
Anegon, Ignacio
影响因子：
6.2
作者：
Menoret, Severine;Ouisse, Laure-Helene;Anegon, Ignacio
通讯作者：
Anegon, Ignacio