Recipient-derived IL-17A protects against GVHD by signaling in recipient tissues without contribution from IL-17E or IL-17B molecules. (A) G-CSF mobilized T-cell replete or TCD BALB/c.WT, BALB/c.IL-17A^−/−, or BALB/c.IL-17RA^−/− donor grafts were transplanted into lethally irradiated B6.WT, B6.IL-17A^−/−, or B6.IL-17RA^−/− mice. Survival is represented by Kaplan-Meier analysis. Combined data from 5 individual experiments are shown. BALB/c.WT → B6.WT (red filled circles; n = 37); BALB/c.WT → B6.IL-17RA^−/− (blue open circles; n = 39); BALB/c.IL-17RA^−/− → B6.IL-17RA^−/− (green filled square; n = 12); BALB/c.IL-17A^−/− → B6.IL-17A^−/− (purple filled inverted triangle; n = 21); BALB/c.WT → B6.IL-17A^−/− (orange filled diamond; n = 20); BALB/c.IL-17A^−/− → B6.WT (green open squares; n = 16); and BALB/c.WT (TCD) → B6.IL-17RA^−/− (lavender filled triangle; n = 14). ****P < .0001, WT vs IL-17A^−/− recipients; ****P < .0001, WT vs IL-17A^−/− recipients transplanted with donor WT or IL-17A^−/−, respectively. (B) G-CSF mobilized BALB/c.WT donor grafts were transplanted into lethally irradiated (B6.WT, red filled circles; B6.IL-17RA^−/−, blue filled squares; B6.IL-17RB^−/−, green open squares; or B6.IL-17RC^−/−, purple filled inverted triangles) recipients (n = 17 to 24 per group). TCD BALB/c.WT grafts were transplanted into lethally irradiated (WT, orange open triangle; IL-17RA^−/−, green open circle; IL-17RC^−/−, lavender open circle) recipients (n = 3 to 7 per TCD group). Survival is represented by Kaplan-Meier analysis. Combined data from 4 replicate experiments are shown. ***P < .0001, WT vs IL-17RA^−/− recipients; ***P < .0001, WT vs B6.IL-17RC^−/− recipients. (C) BALB/c.WT donor BM and luciferase-expressing T cells were transplanted into lethally irradiated B6.WT, B6.IL-17RA^−/−, and B6.IL-17RC^−/− recipients (n = 8 to 9 per group). Animals were imaged at day 6 post-alloSCT and the bioluminescence intensity quantified (photons/sec/cm²/sr × 10⁶). Combined data from 2 replicate experiments are shown. ****P < .0001, WT (red bars) vs IL-17RA^−/− (blue bars); ***P = .0002, WT vs IL-17RC^−/− (green bars). All data are presented as mean ± SEM.