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Inflammasome Components NALP 1 and 3 Show Distinct but Separate Expression Profiles in Human Tissues Suggesting a Site-specific Role in the Inflammatory Response

J. Alain Kummer, Roel Broekhuizen, Helen Everett, Laetitia Agostini, Loes Kuijk, Fabio Martinon, Robin van Bruggen and Jürg Tschopp

Department of Pathology (JAK,RB), Department of Immunology (LK), University Medical Center Utrecht, Utrecht, The Netherlands, and Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Epalinges, Switzerland (HE,LA,FM,RVB,JT)

Correspondence to: Jürg Tschopp, Dept. of Biochemistry, Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland. E-mail: jurg.tschopp{at}unil.ch

Several autoinflammatory disorders such as Muckle–Wells syndrome are characterized by mutations in the NALP3/cryopyrin gene. NALP3 and NALP1 proteins can assemble to inflammasomes that activate caspase-1, resulting in the processing of pro-inflammatory cytokines IL-1ß and IL-18. The present study was designed to determine which cells and tissues express NALP1 and NALP3. Monoclonal antibodies were developed and their use revealed distinct distribution profiles of NALP1 and NALP3. Granulocytes, monocytes (very weakly), dendritic cells, and B and T cells all express NALP1 and NALP3. Highest levels of NALP1 are found in T cells and Langerhans cells. Furthermore, NALP1 is present in glandular epithelial structures such as stomach, gut, lung, and, surprisingly, in neurons and testis. In contrast to NALP1, NALP3 shows a more restricted tissue distribution with expression mainly in non-keratinizing epithelia in the oropharynx, esophagus, and ectocervix. Moreover, NALP3 expression is found in the urothelial layer in the bladder. Likewise, a difference in subcellular distribution between NALP1 and NALP3 is observed because NALP1 is localized mainly in the nucleus, whereas NALP3 is predominantly cytoplasmic. We propose that the presence of NALP3 in epithelial cells lining the oral and genital tracts allows the rapid sensing of invading pathogens, thereby triggering an innate immune response. (J Histochem Cytochem 55:443–452, 2007)

Key Words: autoinflammatory disease • inflammation • mucosa

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