Interleukin‐1 mediates autoreactive CD4+ T cell‐dependent squamous metaplasia in autoimmune dry eye disease

Squamous metaplasia (SQM) of the ocular mucosal epithelia is characterized by aberrant epidermal‐like keratinization, down‐regulated expression of ocular phenotypic marker, Pax6, and loss of mucin‐secreting goblet cells. Using the autoimmune regulator‐deficient ( aire KO) mouse model to mimic the clinical characteristics of autoimmune dry eye disease, we recently provided evidence that the pathogenesis of SQM is driven by targeted destruction of the lacrimal gland and ocular surface tissues by autoreactive CD4+ T helper cells. To further understand the signaling mechanism by which autoreactive T cells promote SQM, we examined organ‐specific T cell infiltrates in IL‐1 receptor 1 ( IL‐1R1 )–sufficient or –deficient SCID recipients following adoptive transfer (AT) of CD4+ T cells from aire KO donors. Interestingly, AT of CD4+ T cells from aire KO mice to IL‐1R1 –sufficient SCID mice led to severe monocytic infiltration in lacrimal and ocular surface tissues with characteristic features of SQM. In contrast, AT of CD4+ cells from aire KO mice to IL‐1R1 –deficient SCIDs caused minimal cellular infiltration of both tissues, with ocular epithelia free of SQM. This work suggests IL‐1 is an essential mediator of ocular SQM in the pathogenesis of CD4+ T cell‐elicited autoimmune dry eye disease. Grant support: NIH R01 EY016203