Abstract
Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC+ innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC+ innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44+ IL-22 producing cells are present in tonsils while NKp44− IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44+ ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44+ ILC are the main ILC subset producing IL-22. NKp44− ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.
Highlights
There is an increasing awareness that early innate response involve several types of RORC+ and RORC− lymphoid-like cells that combine aspects of innate and adaptive immunity including the production of cytokines traditionally associated with adaptive immune cells
The biggest differences in natural cytotoxicity receptors (NCRs) expression between fetal lymph node and tonsils were observed for NKp44 and upon enumeration the percentage of NKp44-expressing RORC+ innate lymphocytes (ILC) was significantly increased in tonsils compared to fetal lymph nodes (Figure 1C)
These data show that the relative distribution of NCR-positive vs NCR-negative ILC is different between tonsils and fetal lymph nodes and follows the pattern described for IL-22 (Cupedo et al, 2009)
Summary
There is an increasing awareness that early innate response involve several types of RORC+ and RORC− lymphoid-like cells that combine aspects of innate and adaptive immunity including the production of cytokines traditionally associated with adaptive immune cells These innate cells are collectively referred to as innate lymphocytes (ILC) and are on the one hand important in early immunity to pathogenic bacteria and helminthes as well as tissue integrity after infection, while these cells on the other hand can be part of pathology during experimental colitis and are expanding in Crohn’s disease patients and allergic rhinosinusitis patients (Satoh-Takayama et al, 2008; Sanos et al, 2009; Buonocore et al, 2010; Moro et al, 2010; Neill et al, 2010; Mjosberg et al, 2011; Spits and Di Santo, 2011).
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