Objective: 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.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.