Th2-M2 polarization in the pathogenesis of adenoid hypertrophy is predominantly characterized by type 2 inflammation

Adenoid hypertrophy (AH) is a common condition in children that can lead to various complications and significantly affect their growth and development. However, the underlying pathogenesis is not fully understood. This study aims to investigate Th2-M2 polarization in the pathogenesis of AH, focusing on a predominant type 2 inflammatory pattern.

We recruited control participants without AH and patients with AH combined with allergic rhinitis (AR), and investigated the predominant inflammatory type in AH with concomitant AR by measuring the Th cell sub-populations and the expression of their key transcription factors, and the levels of type 2 inflammatory factors IL-4 and IL-13 in the adenoid tissue. Additionally, the distribution and quantity of M2 macrophages (M2) in the adenoid tissue were detected to determine their involvement in the pathogenesis of type 2 inflammation-predominant AH. Finally, differentially expressed genes were identified through transcriptome RNA sequencing, followed by their functional validation. A co-culture system of CD68⁺ macrophages and CD4⁺ T cells was established, with IL-4 and dermatophagoides farinae intervention used to explore the role of Th2-M2 polarization in the pathogenesis of type 2 inflammatory predominant AH.

We found that the predominant inflammatory subtypes in AH with concomitant AR were type 2 inflammation and Th17-type inflammation. Further investigation revealed that M2 is involved in the pathogenesis of type 2 inflammation- predominant AH. Transcriptome RNA sequencing identified differentially expressed genes CHI3L2, SOCS1, and STAT6. Functional validation revealed that the Th2-M2 polarization crosstalk promote M2 polarization and may participate in the pathogenesis of AH through the STAT6/SOCS1 pathway. Furthermore, CHI3L2 was found to be highly expressed in the adenoid tissue with a predominant type 2 inflammatory profile. The co-culture of CD68+ macrophages and CD4⁺ T cells along with IL-4 and dermatophagoides farina intervention further validated the sequencing results.

The Th2-M2 polarization may be involved in the pathogenesis of type 2 inflammatory predominant AH, possibly through the STAT6/SOCS1 pathway, which promotes the polarization of M2 macrophages, increases cellular proliferation in the adenoid tissue, and drives the disease process. CHI3L2 was highly expressed in type 2 inflammation-predominant AH and may serve as a promising biomarker candidate for this inflammatory subtype. Further studies are required to determine whether CHI3L2 functionally contributes to adenoid hypertrophy or immune-cell proliferation, which could serve as a therapeutic target.