T-helper (Th)-17 lymphocytes play a crucial role in maintenance and regulation of gut immunity. Our laboratory has demonstrated that acute ethanol (EtOH) exposure before burn injury results in intestinal T cell suppression and enhanced bacterial translocation.
To extend these studies, we examined the effects of EtOH exposure and burn injury on Th17 responses within intestinal lymphoid Peyer's patches (PP). We further investigated whether restitution of interleukin (IL)-23 enhances PP cell IL-17 and IL-22 after EtOH and burn injury.
Male mice, approximately 25 g, were gavaged with EtOH (2.9 mg/kg) before receiving an approximately 12.5% total body surface area full thickness burn. One day postinjury, PP mixed cells were cultured in the presence of plate-bound anti-CD3/soluble anti-CD28 in the presence or absence of IL-23 for 48 hours. Supernatants were harvested for IL-17 and IL-22 levels.
When combined with EtOH intoxication, burn injury significantly decreased IL-17 and IL-22, as compared with sham injury. IL-23 treatment successfully increased levels of IL-22 but not IL-17. This restoration was prevented when PP cells were treated with CH-223191, an aryl hydrocarbon receptor inhibitor. To further delineate the mechanism of differential IL-17 and IL-22 suppression, PP cells were treated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, which signal via protein kinase C (PKC) and calcium flux. Treatment with PMA and ionomycin significantly prevented the decrease in IL-17 but not IL-22 after EtOH exposure and burn injury.
These findings suggest that IL-23-mediated restoration of IL-22 is aryl hydrocarbon receptor dependent, whereas IL-17 requires activation of protein kinase C and intracellular calcium signaling.
Ethanol and burn injury suppresses CD3-dependent interleukin (IL)-17 and IL-22 from Peyer's patch cells. Exogenous IL-23 restitution restores IL-22 levels. IL-23 mediated restoration of IL-22 is modulated by the aryl hydrocarbon receptor, whereas restoration of IL-17 requires activation of protein kinase C and intracellular calcium flux.
From the Alcohol Research Program, Burn & Shock Trauma Research Institute, Department of Surgery and Department of Microbiology and Immunology, Cell Biology, Neurobiology & Anatomy Program, Loyola University Chicago Health Sciences Division, Maywood, IL.
Reprints: Mashkoor A. Choudhry, PhD, Burn & Shock Trauma Research Institute, Bldg 110/EMS; Room 4236, Loyola University Health Sciences Division, 2160 South First Ave, Maywood, IL 60153. E-mail: firstname.lastname@example.org.
Disclosure: Supported by NIH grants R01AA015731 (MAC) and R01AA015731-04S1 (MAC). Juan L. Rendon is supported by NIH grants F30AA020167 (JLR), T32AA013527 (EJK), the Loyola University Chicago Stritch School of Medicine Combined MD/PhD Program, and the Dr Ralph and Marian C. Falk Medical Research Trust. The authors declare that they have no competing interests.