肠粘膜必须平衡对共生微生物和管腔抗原的耐受性，并快速检测肠道病原体，以维持体内平衡。通过先天免疫受体调节上皮层完整性来促进这种平衡。肠上皮细胞中表达的某些 NOD 样受体 (NLR)，包括 NLRC4 和 NLRP9B，可形成炎症小体，通过激活 caspase-1 导致受感染细胞挤出来抵御病原体。 NLRP1B 是一种鼠类 NLR，由与人 NLRP1 同源的高度多态性基因的五个等位基因编码。 NLRP1B 会形成炎症小体，以响应多种引起肠道感染的病原体，但它几乎完全在免疫细胞中进行研究，尚未在肠上皮细胞中进行表征。在这里，我们表明 Nlrp1b 在 C57BL/6J 小鼠的回肠和结肠类器官中表达。 Nlrp1b 被类器官中的白细胞介素 13 和体内的原生动物鼠三滴虫上调，表明 NLRP1B 可能参与防御肠道寄生虫。令人惊讶的是，虽然 Val-boro-Pro (VbP) 激活骨髓源性巨噬细胞中的 NLRP1B，但它不会激活类器官中的 NLRP1B。此外，我们没有在 Balb/cJ 小鼠的类器官中检测到 Nlrp1b，该类器官表达的等位基因与 C57BL/6J 小鼠中表达的等位基因不同。总之，我们的结果表明，NLRP1B 在小鼠 IEC 中可能具有等位基因依赖性功能，其调节与巨噬细胞的调节不同。版权所有 © 2024。由 Elsevier Masson SAS 出版。

The intestinal mucosa must balance tolerance to commensal microbes and luminal antigens with rapid detection of enteric pathogens in order to maintain homeostasis. This balance is facilitated through the regulation of epithelial layer integrity by innate immune receptors. Certain NOD-like receptors (NLRs) expressed in intestinal epithelial cells, including NLRC4 and NLRP9B, form inflammasomes that protect against pathogens by activating caspase-1 to cause extrusion of infected cells. NLRP1B is a murine NLR encoded by five alleles of a highly polymorphic gene homologous to human NLRP1. NLRP1B forms inflammasomes in response to a variety of pathogens that cause intestinal infections, but it has almost exclusively been studied in immune cells and has not been characterized in cells of the intestinal epithelium. Here, we show that Nlrp1b is expressed in ileal and colonic organoids derived for C57BL/6J mice. Nlrp1b was upregulated by interleukin-13 in organoids and by the protozoan Tritrichomonas muris in vivo, suggesting that NLRP1B may be involved in defense against enteric parasites. Surprisingly, while Val-boro-Pro (VbP) activated NLRP1B in bone marrow-derived macrophages, it did not activate NLRP1B in organoids. We furthermore did not detect Nlrp1b in organoids derived from Balb/cJ mice, which express a different allele than the one expressed in C57BL/6J mice. Together, our results suggest that NLRP1B may have an allele-dependent function in murine IECs whose regulation is distinct from that of macrophages.Copyright © 2024. Published by Elsevier Masson SAS.