Desmoglein-4 deficiency weakens OVA specific IgA and IgM humoral immunity

VIRUEL LUCIANA BELÉN; SÁNCHEZ MARÍA BELÉN; MICHEL MARÍA CECILIA; TRONCOSO MARIANA; NEIRA FLAVIA JUDITH; CAMPO-VERDE-ARBOCCÓ FIORELLA; SOAJE MARTA; SÁNCHEZ MARÍA VICTORIA; PIETROBON ELISA OLIVIA; INNOCENTI ALICIA CAROLINA; JAHN GRACIELA ALMA; VALDEZ SUSANA RUTH; MACKERN-OBERTI JUAN PABLO

Congreso; XL Reunión Anual de la Sociedad de Biología de Cuyo; 2022

Desmogleins (Dsg) are cadherin-type proteins involved in the adhesion mechanisms carried out by desmosomes. Dsg-4 deficiency is associated with hair follicle alterations and hair loss in humans, mice, and rats. Recently, we have reported that the imiquimod topic administration to Dsg-4 deficient rats leads to an exacerbated skin inflammation compared to healthy control animals. Unfortunately, the role of Dsg-4 in IgA and IgM humoral immunity has not been addressed. The focus of our work was to determine whether desmoglein 4 deficiency impairs OVA-specific IgA and IgM induction. For this purpose, Desmoglein 4 deficient rats OFA hr/hr (Dsg4 null) and wild-type Sprague Dawley (SD) rats were inoculated intradermal with 20µg/40µl OVA/PBS. Two weeks later, serum samples were obtained to determine OVA-specific IgA and IgM levels by ELISA. Surprisingly, Dsg4 null rats displayed lower OVA-specific IgM (OD at 1/100; Dsg4 null 0.152±0.053 vs SD 0.427±0.194, t test, p=0.0383) and IgA levels compared to SD group (OD at 1/100; Dsg4 null 0.094±0.021 vs SD 0.1736±0.025, t test, p=0.0383). When we evaluated axillar lymphatic nodes expansion after topic imiquimod administration for 3 consecutive days every week for 2 weeks, we found that Dsg4 null rats displayed a lymphatic node weight increased compared to SD rats (imiquimod Dsg4 null 375mg ± 27 vs imiquimod SD 185mg ± 25, t test, p=0.0043; untreated Dsg 4 null 58mg ±3 and SD 43 mg ±6). These results suggest that desmoglein-4 may help in mounting specific humoral immunity. Several mechanisms may be involved including antigen lymphatic drainage, keratinocyte-derived cytokines, aberrant crosstalk between keratinocyte and dendritic cells, leading to an impaired germinal center reaction. Although further research is needed, our results assign a new role to Dsg-4 in inducing humoral immunity during an intradermal antigen exposure.