Housing conditions affect enterocyte death mode and turnover rate in mouse small intestine

Small intestinal enterocytes are continuously renewed. Shedding/death of enterocytes involves receptor-interacting protein kinase 1 (RIPK1)-dependent (but RIPK3-independent) necrotic death, but the regulatory mechanism of the processes is not fully understood. Here, we show that mouse housing conditions, such as the type of bedding material and the presence or absence of a Shepherd Shack, affect enterocyte turnover rate and determine whether enterocyte shedding/death is RIPK1-independent or -dependent. Mice housed with ALPHA-dri (αDri, hard paper chip) bedding material without a Shepherd Shack had a higher, largely RIPK1-dependent enterocyte turnover rate and higher blood corticosterone levels, suggesting the involvement of minor stress, whereas mice housed with αDri plus a Shepherd Shack or with Soft Chip had a lower, RIPK1-independent turnover rate and lower blood corticosterone levels. Corticosterone administration to a small intestine culture derived from mice housed with αDri plus a Shepherd Shack or with Soft Chip increased enterocyte shedding/death and turnover. By using kinase inhibitors and knockout mice, we showed that the switch from RIPK1-independent to RIPK1-dependent enterocyte shedding/death and turnover involves suppression of TANK-binding kinase 1. Our results demonstrate that housing conditions may cause minor stress, which alters the mode of enterocyte shedding/death and enterocyte turnover rate in mice.