Genetic deficiencies of both IL-4 receptor alpha chain and IL-10 trigger early onset of severe colitis in mice

IF 3.7 4区医学 Q2 CELL BIOLOGY

Cellular immunology Pub Date : 2023-11-01 DOI:10.1016/j.cellimm.2023.104779

Hisashi Nagase , Masaya Takamoto , Nancy Noben-Trauth

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Abstract

Inflammatory bowel diseases are associated with dysregulated inflammatory immune responses in the gastrointestinal tract. We found that deficiencies of both IL-4 receptor alpha chain (IL-4Rα) and IL-10 in BALB/c mice (IL-4Rα × IL-10 KO mice) highly induced spontaneous rectal prolapse and diarrhea. These mice also exhibited severe colitis in their cecum and colon and marked elevation of serum proinflammatory cytokines including TNFα and IFNγ. These pathologies were transmittable with their cecal contents containing Helicobacter spp. Their mesenteric LN cells produced TNFα and IFNγ in response to soluble H. hepaticus antigens and high titers of H. hepaticus-specific serum IgG were also detected. These results suggested the important function of IL-4Rα signaling in controlling the intestinal inflammation and the susceptibility to intestinal microbes including H. hepaticus. Therefore, these IL-4Rα × IL-10 KO mice potentially provide the significant murine model for clarifying the causes and control of spontaneous colitis and intestinal inflammation.

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IL-4受体α链和IL-10的遗传缺陷都会引发小鼠严重结肠炎的早期发作。

炎症性肠病与胃肠道炎症免疫反应失调有关。我们发现，BALB/c小鼠（IL-4Rα×IL-10 KO小鼠）中IL-4受体α链（IL-4Rα）和IL-10的缺乏高度诱导自发性直肠脱垂和腹泻。这些小鼠的盲肠和结肠也表现出严重的结肠炎，血清促炎细胞因子（包括TNFα和IFNγ）显著升高。这些疾病可通过盲肠内容物中含有幽门螺杆菌传播。它们的肠系膜LN细胞对可溶性肝吸虫抗原产生TNFα和IFNγ，并检测到高滴度的肝吸虫特异性血清IgG。这些结果表明，IL-4Rα信号传导在控制肠道炎症和对包括肝吸虫在内的肠道微生物的易感性方面具有重要作用。因此，这些IL-4Rα×IL-10 KO小鼠可能为阐明自发性结肠炎和肠道炎症的原因和控制提供了重要的小鼠模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular immunology 生物-免疫学

CiteScore

8.20

自引率

2.30%

发文量

102

审稿时长

30 days

期刊介绍： Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.