Aiko I. Klingler

Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois

CRSsNP is a heterogenous disease but type 2 inflammation in CRSsNP was more common than type 1 inflammation among patients in Chicago, Illinois. Distinct therapeutic strategies may be needed depending on the type of inflammation found in CRSsNP.

Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines. However, the presence of various types of ILC in CRS is poorly understood.

Proprotein convertases generate a highly functional heterodimeric form of thymic stromal lymphopoietin in humans

Rationale: Thymic stromal lymphopoietin (TSLP) is known to be elevated and truncated in nasal polyps (NPs) of patients with chronic rhinosinusitis and might play a significant role in type 2 inflammation in this disease. However, neither the structure nor the role of the truncated products of TSLP has been studied. Objective: We sought to investigate the mechanisms of truncation of TSLP in NPs and the function of the truncated products. Methods: We incubated recombinant human TSLP with NP extracts, and determined the protein sequence of the truncated forms of TSLP using Edman protein sequencing and matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry. We investigated the functional activity of truncated TSLP using a PBMC‐based bioassay. Results: Edman sequencing and mass spectrometry results indicated that NP extracts generated 2 major truncated products, TSLP (residues 29–124) and TSLP (131–159). Interestingly, these 2 products remained linked with disulfide bonds and presented as a dimerized form, TSLP (29–124 + 131–159). We identified that members of the proprotein convertase were rate‐limiting enzymes in the truncation of TSLP between residues 130 and 131 and generated a heterodimeric unstable metabolite TSLP (29–130 + 131–159). Carboxypeptidase N immediately digested 6 amino acids from the C terminus of the longer subunit of TSLP to generate a stable dimerized form, TSLP (29–124 + 131–159), in NPs. These truncations were homeostatic but primate‐specific events. A metabolite TSLP (29–130 + 131–159) strongly activated myeloid dendritic cells and group 2 innate lymphoid cells compared with mature TSLP. Conclusions: Posttranslational modifications control the functional activity of TSLP in humans and overproduction of TSLP may be a key trigger for the amplification of type 2 inflammation in diseases.