Investigating diversified TGFbeta signaling pathways in the regulation of skin Langerhans cells

Langerhans cells (LCs), the skin residing dendritic cells (DCs), control both adaptive immunity and immune tolerance in skin. Transforming growth factor-β1 (TGFβ1) is recognized as a critical factor influencing LC maintenance and function, and TGFβ1 signals through the interaction of TGFβ receptors to activate distinct intracellular canonical Smad2/3/4 and non-canonical Smad-independent pathways. But detailed TGF signaling pathways involved in LC regulation remain elusive. Using mouse models with spatial- and temporal-specific mutations in TGF receptors and related signaling molecules, this project aims to elucidate the context-dependent specificities of TGFβ signaling pathways and the molecular mechanisms governing the regulation of LC embryonic ontogeny, postnatal homeostasis, function, and inflammation-induced repopulation.

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Selected Publications

1. Xu YP, Shi YL, Li L. Et al. TGFβ/Smad3 Pathway is not required for epidermal Langerhans cell development. J Invest Dermatol, 2012; 132(8):2106-9

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2. Zhang X, Gu J, Yu FS. Et al. (2016) TGF-β1-induced transcription factor networks in Langerhans cell development and maintenance. Allergy. 2016; 71(6):758-64.

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3. Huang L, Li GH, Yu Q. et al. Smad2/4 Signaling Pathway Is Critical for Epidermal Langerhans Cell Repopulation Under Inflammatory Condition but Not Required for Their Homeostasis at Steady State. Front Immunol. 2020 May 7;11:912. PMID: 32457763

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4.Yu Q, Parajuli N, Yi Q, et al. ALK3 Is Not Required for the Embryonic Development, Homeostasis, and Repopulation of Epidermal Langerhans Cells in Steady and Inflammatory States. J Invest Dermatol. 2021 Jul; 141(7):1858-1861.  PMID: 33359325