Intranasal streptococcal infection exacerbates psoriasis-like dermatitis via the induction of skin tissue-resident memory T cells

Recurrent streptococcal tonsillitis exacerbates psoriasis. Studies have indicated that T cells responding to streptococcal antigens in the skin are involved in the pathogenesis of the disease. However, a direct link between streptococcal tonsillitis and psoriasis has not been evidenced. In the present study, the impact of intranasal (i.n.) streptococcal infection on psoriasis was investigated using the imiquimod (IMQ) psoriasis mouse model. The results showed that repeated i.n. infection with group A Streptococcus (GAS) induced a robust and persistent Th17 response in the nasal-associated lymphoid tissue (NALT) and exacerbated IMQ-mediated psoriatic skin lesions. ELISpot and flow cytometry analyses revealed that GAS-reactive tissue-resident memory T cells (TRM) were present in the skin of GAS-infected mice and produced IL-17/IL-23 axis cytokines in response to IMQ, compared to mice uninfected with GAS. In addition, i.n. infection with Streptococcus pneumoniae (Sp), a pathogen not associated with the development of psoriasis, also induced a persistent Th17 response in NALT but did not exacerbate IMQ-induced psoriatic inflammation nor elicited Sp-specific T cells in the skin. The results provide in vivo evidence that GAS-associated psoriasis is dependent on the skin GAS-specific TRM cells induced by GAS nasopharyngeal infection and can be later activated by environmental triggers, leading to psoriatic inflammation. Reducing the reservoir of Th17 cells, which are source of skin TRM cells, may constitute a promising treatment for psoriasis.