The Contribution of Immunoglobulin G to Inflammation is Regulated by The Site of Production via Glycosylation

Yıl 2025, Cilt: 41 Sayı: 3, 918 - 935, 31.12.2025

Altan Ercan

https://doi.org/10.65520/erciyesfen.1789878

https://izlik.org/JA74NN42HA

Öz

Immunoglobulin G (IgG) is one of the main contributors to inflammation due to its function and amount in circulation. This function of IgG can swing from pro- to anti-inflammatory states with small changes in glycan structure at Asparagine-297 of IgG Fc domain. This variation is implicated in pathophysiology of autoimmune diseases such as rheumatoid arthritis. Although our understanding about the structure-function relation of IgG Fc glycosylation has immensely increased for the last four decades, it is still limited about the regulators of this glycan structure. To broaden our understanding, ex-vivo cell cultures derived from lymph node (LN), spleen (SP) and bone marrow (BM) of K/BxN mouse, which is a model for autoantibody-dependent rheumatoid arthritis, were established. The glycan structures of antigen purified anti-glucose-6-phosphate isomerase (anti-GPI) autoantibody heavy chains produced in these cultures were characterized using HPLC. According to the results, while IgG produced in LN is decorated with the highest amount of pro-inflammatory agalactosylated structure, IgG produced in SP has the highest amount of anti-inflammatory sialylated structure. Interestingly, IgG produced in BM stands in between them due to more balanced distribution of glycan structures. In conclusion, the ex-vivo cell cultures of LN, SP and BM were successfully established, and the contribution of IgG to on-going inflammation is regulated by the production site of anti-GPI autoantibody via glycan structures. In addition, N-glycan profile of anti-GPI autoantibody produced in LN closely replicates the N-glycan profile for anti-GPI autoantibody from K/BxN serum indicating that anti-GPI autoantibody in circulation is heavily produced in LN.

Anahtar Kelimeler

Immunoglobuin G , IgG , Rheumatoid arthritis , Inflammation , Sialylation , Galactosylation , Pro-inflammatory , Anti-inflammatory , Glycosylation

İmmünoglobulin G'nin İnflamasyona Katkısı, Glikozilasyon Yoluyla Üretim Yeri Tarafından Düzenlenir

https://izlik.org/JA74NN42HA

Öz

İmmünoglobulin G (IgG), işlevi ve dolaşımdaki miktarı nedeniyle inflamasyona katkıda bulunan başlıca faktörlerden biridir. IgG'nin bu işlevi, IgG Fc bölgesindeki Asparagin-297 glikan yapısındaki küçük değişikliklerle pro-inflamatuar durumdan anti-inflamatuar duruma geçebilmektedir. IgG Fc glikozilasyonunun yapı-fonksiyon ilişkisi hakkındaki bilgi son kırk yılda büyük ölçüde artmış olsa da, bu glikan yapısının düzenleyicileri hakkında hala sınırlıdır. Anlayışımızı genişletmek için, otoantikor bağımlı romatoid artrit modeli olan K/BxN faresinin lenf nodu (LN), dalak (SP) ve kemik iliğinden (BM) türetilen ex-vivo hücre kültürleri oluşturuldu. Bu kültürlerde üretilen antijen ile saflaştırılmış olan anti-glikoz-6-fosfat izomeraz (anti-GPI) otoantikor ağır zincirlerinin glikan yapıları HPLC kullanılarak karakterize edildi. Sonuçlara göre, LN'de üretilen IgG en yüksek miktarda pro-inflamatuar agalaktosile yapıya sahipken, SP'de üretilen IgG en yüksek miktarda anti-inflamatuar siyalile yapıya sahiptir. İlginç bir şekilde, BM'de üretilen IgG, glikan yapılarının daha dengeli dağılımı nedeniyle bunların arasında yer almaktadır. Sonuç olarak, LN, SP ve BM'nin ex-vivo hücre kültürleri başarıyla oluşturulmuştur ve IgG'nin devam eden inflamasyona katkısı, glikan yapıları aracılığıyla anti-GPI otoantikorunun üretim bölgesi tarafından düzenlenmektedir. Ayrıca, LN'de üretilen anti-GPI otoantikorunun N-glikan profili, K/BxN serumundan elde edilen anti-GPI otoantikorunun N-glikan profiliyle yakından örtüşmektedir; bu da dolaşımdaki anti-GPI otoantikorunun LN'de yoğun olarak üretildiğini göstermektedir.

Anahtar Kelimeler

Immunoglobuin G , IgG , Rheumatoid arthritis , Inflammation , Sialylation , Galactosylation , Pro-inflammatory , Anti-inflammatory , Glycosylation

Kaynakça

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