Effect and mechanism of anti-CD122 antibody on psoriasis-like skin lesions in mice
Objective To explore the effect and mechanism of anti-CD122 antibody on psoriasis-like skin lesions in mice.Methods The study was conducted from July 1 to November 23,2020.A total of 56 BALB/c female mice were randomly assigned to four groups:a vaseline control group(blank control group),an imiquimod model group(model group),an isotype control antibody experimental group(experimental group A),and an anti-CD122 antibody experimental group(experimental group B).The dynamic changes of psoriasis-like skin lesions were observed using the Psoriasis Area and Severity Index(PASI)score;the pathological changes of skin lesion tissues were observed under the microscope and the thickness of the epidermal layer was measured;the phenotypes and changes of TRM cells in skin lesions were detected using the immunofluorescence double-labeling method;the expressions and changes of interleukin(IL)-15 and IL-17A in skin lesions were detected using the immunohistochemical method.Independent sample t test was used for the measurement data.Results The immunofluorescence double-labeling showed that the number of TRM cells in the initial lesions(3 and 6 days)of the model group[CD3+CD103+:(16.40± 1.43)cell count/field of view,(29.80±2.28)cell count/field of view;CD4+CD103+:(10.80± 1.77)cell count/field of view,(16.20±1.28)cell count/field of view;CD8+CD103+:(15.10± 1.65)cell count/field of view,(26.05±1.43)cell count/field of view;CD122+CD103+:(16.52± 1.43)cell count/field of view,(26.80±1.40)cell count/field of view]were higher than those in control group(all P<0.01).The number of TRM cells in the initial(3 and 6 days)and re-stimulated(38 and 41 days)lesions of the experimental group B were lower than those in the model group and the experimental group A at the same time(all P<0.05),with CD8+TRM cells predominantly reduced(P<0.01).The immunohistochemical results showed that the expressions of IL-15 and IL-17A in the initial lesions(38 and 41 days)of the model group[(115.66±3.69)IOD/area,(121.65±3.36)IOD/area,(104.30±3.47)IOD/area,and(59.87±3.20)IOD/area]were higher than those of the control group[(28.15±2.25)IOD/area,(28.05±2.15)IOD/area,(2 5.63±2.10)IO D/area,and(25.01±2.71)IO D/area],with statistically significant differences(all P<0.05).The expressions of IL-15 and IL-17A in the initial(3 and 6 days)and re-stimulated(38 and 41 days)lesions of the experimental group B were lower than those of the model group and experimental group A at the same time(all P<0.05).Conclusions TRM cells,IL-15,and IL-17A might be involved in the occurrence and development of psoriasis-like skin lesions in mice.Anti-CD122 antibody can improve psoriasis-like lesions in mice,and this effect might be related to its inhibition of formation and function of TRM cells,mainly CD8+TRM cells,as well as the reduction of IL-15 and IL-17A expressions.
PsoriasisCD122Tissue resident memory T cellsInterleukin-15Interleukin-17AAnimalexperiment