T cells regulate lymph node-resident ILC populations in a tissue and subset-specific way

Area of Science:

• Immunology
• Cell Biology

Background:

• Innate lymphoid cells (ILCs) are crucial immune cells found in various tissues, including the small intestine lamina propria and secondary lymphoid organs (SLOs).
• The regulation of ILCs by adaptive immunity within SLOs, particularly mesenteric lymph nodes (MLNs) and peripheral lymph nodes (PLNs), is not fully understood.
• T cell deficiency leads to altered ILC subset distribution, with increased ILC2s in MLNs and increased CCR6+ ILC3s in PLNs.

Purpose of the Study:

• To investigate how T cells and adaptive immunity regulate tissue-resident innate lymphoid cells (ILCs) within secondary lymphoid organs (SLOs).
• To determine the role of microbial colonization in modulating ILC populations in the context of T cell deficiency.
• To elucidate the mechanisms by which T cells control specific ILC subsets in different lymph node compartments.

Main Methods:

• Comparative analysis of ILC populations in T cell-deficient and T cell-reconstituted mice.
• Manipulation of microbial colonization from birth to assess its impact on ILCs.
• Flow cytometry and cytokine analysis to characterize ILC subsets and their regulation.

Main Results:

• T cells exert tissue- and subset-specific regulation on lymph node-resident ILCs.
• Reducing microbial colonization restored CCR6+ ILC3s in MLNs of T cell-deficient mice.
• T cell reconstitution decreased MLN ILC2s and PLN ILC3s, independent of microbial colonization status.
• Stromal IL-33, acting via T cells, partially regulates the accumulation of MLN ILC2s.

Conclusions:

• Adaptive immunity, particularly T cells, plays a critical role in shaping innate lymphoid cell populations within SLOs.
• Microbial colonization influences ILC subset distribution, especially in the context of T cell deficiency.
• T cell-mediated regulation of ILCs is compartmentalized, affecting different ILC subsets in MLNs and PLNs distinctly, partly through IL-33 signaling.