Paneth cells are the primary source of C-type lysozyme, a β-1,4-N-acetylmuramoylhydrolase that enzymatically processes bacterial cell walls. Paneth cells are normally present in human cecum and ascending colon, but are rarely found in descending colon and rectum; Paneth cell metaplasia in this region and aberrant lysozyme production are hallmarks of inflammatory bowel disease (IBD) pathology. Here, we examined the impact of aberrant lysozyme production in colonic inflammation. Targeted disruption of Paneth cell lysozyme (Lyz1) protected mice from experimental colitis. Lyz1-deficiency diminished intestinal immune responses to bacterial molecular patterns and resulted in the expansion of lysozyme-sensitive mucolytic bacteria, including Ruminococcus gnavus, a Crohn’s disease-associated pathobiont. Ectopic lysozyme production in colonic epithelium suppressed lysozyme-sensitive bacteria and exacerbated colitis. Transfer of R. gnavus into Lyz1^−/− hosts elicited a type 2 immune response, causing epithelial reprograming and enhanced anti-colitogenic capacity. In contrast, in lysozyme-intact hosts, processed R. gnavus drove pro-inflammatory responses. Thus, Paneth cell lysozyme balances intestinal anti- and pro-inflammatory responses, with implications for IBD.

Paneth 细胞是 C 型溶菌酶的主要来源，C 型溶菌酶是一种 β-1,4-N-乙酰胞壁酰水解酶，可通过酶处理细菌细胞壁。Paneth细胞通常存在于人类盲肠和升结肠中，但在降结肠和直肠中很少发现；该区域的潘氏细胞化生和异常的溶菌酶产生是炎症性肠病 (IBD) 病理学的标志。在这里，我们检查了异常溶菌酶产生对结肠炎症的影响。Paneth 细胞溶菌酶 ( Lyz1 ) 的靶向破坏保护小鼠免于实验性结肠炎。Lyz1 缺乏会减弱肠道对细菌分子模式的免疫反应，并导致对溶菌酶敏感的粘液溶解细菌（包括Ruminococcus gnavus）的扩增，克罗恩病相关的病原体。结肠上皮异位溶菌酶的产生抑制了溶菌酶敏感的细菌并加剧了结肠炎。将R. gnavus转移到Lyz1 ^-/-宿主引发 2 型免疫反应，导致上皮重编程和增强的抗结肠形成能力。相比之下，在溶菌酶完整的宿主中，加工过的R. gnavus驱动了促炎反应。因此，潘氏细胞溶菌酶平衡肠道抗炎和促炎反应，对 IBD 有影响。