T cell-specific deficiency in BBSome component BBS1 interferes with selective immune responses

Area of Science:

• Immunology
• Genetics
• Cell Biology

Background:

• Bardet-Biedl syndrome (BBS) involves genetic defects affecting BBS proteins, linked to immune and inflammatory conditions.
• BBS1, a BBSome component, influences immune synapse assembly and centrosome polarization in antigen-presenting cells.

Purpose of the Study:

• To investigate the role of the BBSome in T cell function by examining mice with a specific T cell deletion of the Bbs1 gene.
• To determine the impact of Bbs1 gene deletion in T cells on immune cell populations, T cell responses, and skin wound healing.

Main Methods:

• Generated T cell-specific Bbs1 knockout mice (T-BBS1-/-).
• Analyzed spleen and lymph node cellularity, thymocyte development (CD4/CD8 lineage), and splenocyte populations post-Imiquimod treatment.
• Assessed skin wound closure rates in T-BBS1-/- mice, comparing males and females.

Main Results:

• T-BBS1-/- mice showed smaller spleens but maintained normal body weight, adiposity, and glucose metabolism.
• No significant changes were observed in B cell or T cell proportions/numbers in spleen and lymph nodes, nor in thymic CD4/CD8 lineage commitment.
• Imiquimod treatment led to a higher percentage of CD3+ splenocytes, specifically CD4 T cells, in T-BBS1-/- mice.
• T-BBS1-/- mice exhibited significantly delayed wound closure, particularly in males, indicating impaired T cell-mediated skin repair.

Conclusions:

• The BBSome, through BBS1, plays a critical role in regulating specific T cell functions, including immune responses and skin repair.
• Disruption of Bbs1 in T cells affects T cell responses to immune stimuli and significantly impairs wound healing capabilities.
• These findings highlight the BBSome as a key regulator in T cell-mediated tissue repair processes.