Figure 2.

MCL1 deficiency–associated chronic inflammation is mediated by ILCs. (A) Genetic depletion of Rag1 within Mcl1^ΔIEC mice significantly reduced weight gain and survival (n = 19). Blue asterisk: Mcl1^ΔIEC mice compared with littermate controls, red asterisk: Mcl1^ΔIECRag1^−/− mice compared with littermate controls, purple asterisk: Mcl1^ΔIEC mice compared with Mcl1^ΔIECRag1^−/− mice. (B) Representative images from the colon of 2-month-old Rag1^−/− control mice compared with Mcl1^ΔIECRag1^−/− mice showing impaired intestinal architecture (hematoxylin and eosin [H&E]), increased IEC apoptosis (cl. casp. 3) and hyperproliferation (Ki-67) (scale bars: 100 μm, 25 μm-inserts). (C) Blinded histological scores comparing 2-month-old Mcl1^ΔIECRag1^−/− mice with Rag1^−/− mice (n = 5). (D) Colon cultures established from 2-month-old mice and analyzed using multiplex analysis (minimum n = 8 per group). (E) Representative images from colons of 3-month-old Mcl1^ΔIECRag1^−/− mice following 4 weeks of α-Thy1.2 depleting antibody or corresponding isotype administration (scale bars: 100 μm, 25 μm-inserts). (F) Colon cultures established from 3-month-old mice and analyzed for TNF-α, IL-22, IL-23A, IL-17A, IL-17F, and IL-1β expression using multiplex analysis (minimum n = 8 per group). Data presented as either bar charts or scatter plot graph show mean values ± SEM. Statistical analyses were conducted by 1-way analysis of variance with Bonferroni correction (A [body weight], D and F), log rank (Mantel-Cox test) (A, survival) or Mann-Whitney test (C) where ∗P ≤ .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001.